Periaqueductal Gray


In both groups the perception of others in pain was associated with activation of the pain matrix, including the ACC, insula, somatosensory cortex, supplementary motor area and periaqueductal gray.  

Central amygdala nucleus (CeA)-periaqueductal gray (PAG) pathway is the component of descending antinociceptive circuitry.  

The analgesic effects of morphine are mediated, in part, by periaqueductal gray (PAG) neurons that project to the rostral ventromedial medulla (RVM).  

Five general brain regions contained retrogradely labeled neurons: cerebral cortex (infralimbic and insular regions), rostral forebrain structures (subfornical organ, organum vasculosum of the lamina terminalis, taenia tecta, nucleus accumbens, lateral septum, endopiriform nucleus, dorsal BST, substantia innominata, and, most prominently the amygdala-primarily its basomedial and central subnuclei), thalamus (central medial, intermediodorsal, reuniens, and, most prominently the paraventricular thalamic nucleus), hypothalamus (medial preoptic area, perifornical, arcuate, dorsomedial, parasubthalamic, and posterior hypothalamic nuclei), and brainstem (periaqueductal gray matter, dorsal and central superior raphe nuclei, parabrachial nucleus, pre-locus coeruleus region, NTS, and A1 noradrenergic neurons in the caudal ventrolateral medulla).  

Several other regions were labeled including the parts of the amygdala, periaqueductal gray, lateral parabrachial nucleus and deep cerebellar nuclei.  

Unrestrained KO mice exhibited significantly lower c-Fos levels relative to unrestrained WT mice in 9 regions, including lateral septum and periaqueductal gray.  

Evidences from studies using electrical or chemical stimulation of the midbrain periaqueductal gray (PAG) suggest that whereas the dorsal PAG is critical for the regulation of panic-related defensive behaviors, the ventrolateral PAG (vlPAG) modulates generalized anxiety-related responses. In the present study we evaluated whether the activation of 5-HT1A and 5-HT2A/2C receptors in the ventrolateral column of the periaqueductal gray (vlPAG) causes differential effects on an anxiety- and a panic-related defensive behavior, respectively, inhibitory avoidance and escape, in male Wistar rats submitted to the elevated T-maze.  

Glutamate-NMDA (N-methyl-d-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction.  

In this review we focus on 2 of them, the periaqueductal gray matter and nucleus raphe magnus.  

The periaqueductal gray (PAG) is involved in many gonadal steroid-sensitive behaviors, including responsiveness to pain.  

The MPL has afferent neuronal connections distinct from adjacent brain regions including major inputs from the auditory cortex, medial part of the medial geniculate body, superior colliculus, external and dorsal cortices of the inferior colliculus, periolivary area, lateral preoptic area, hypothalamic ventromedial nucleus, lateral and dorsal hypothalamic areas, subparafascicular and posterior intralaminar thalamic nuclei, periaqueductal gray, and cuneiform nucleus.  

We examined the role of eNOS within the dorsolateral periaqueductal gray mater (dlPAG) on cardiovascular responses along with glutamate and GABA concentrations during mechanical-, heat-, and cold-induced nociception in anesthetized rats.  

Cannabinoids and opiates inhibit pain, in part, by activating the periaqueductal gray (PAG).  

These regions included the periaqueductal gray, an area that plays an important role in morphine-induced analgesia but also in the development of tolerance to morphine.  

Activation of cannabinoid CB(1) receptors in the dorsolateral periaqueductal gray induces anxiolytic-like effects in the elevated plus maze. Male Wistar rats (n=5-9/group) with cannulae aimed at the dorsolateral periaqueductal gray were water deprived for 24 h and pre-exposed to the apparatus where they were allowed to drink for 3 min. The results give further support to the proposal that facilitation of CB(1) receptor-mediated endocannabinoid neurotransmission in the dorsolateral periaqueductal gray modulates defensive responses..  

Next, we investigated how pharmacological blockade of the PMd interferes with the conditioned behavioral responses to a context previously associated with a predator, and how this blockade affects the activation pattern of periaqueductal gray (PAG) sites likely to organize the conditioned behavioral responses to the predatory context.  

It has been suggested that a neural circuit responsible for the production of defensive behavior elicited by the dorsal periaqueductal gray (dPAG) stimulation may project through ascending fibers to forebrain structures such as the basolateral complex of the amygdala (BLA).  

The midbrain periaqueductal gray (PAG) is involved in organizing behavioral responses to threat, stress, and pain.  

The formalin stimulation at the hind paw of rats resulted in significant metabolic increases in the bilateral cingulate cortex, motor cortex, primary somatosensory cortex, secondary somatosensory cortex, insular cortex, visual cortex, caudate putamen, hippocampus, periaqueductal gray, amygdala, thalamus, and hypothalamus.  

Several neurotransmitters, including glutamate and serotonin, modulate defensive behaviors related to anxiety in the rat dorsal periaqueductal gray (PAG).  

Then, NT-I-NPs were administered intranasally or intravenously to rats and the radioactivities in periaqueductal gray (PAG) were monitored up to 240 min utilizing the microdialysis sampling technique.  

LR animals did not however yield any significant difference in mu opioid receptor mRNA levels in locus coeruleus (LC), ventral periaqueductal gray (vPAG), nucleus raphe magnus (NRM) and nucleus reticularis paragigantocellularis (NRPG) between these two groups of animals.  

Similar injection of muscimol into the caudal region of the lateral/dorsolateral periaqueductal gray (l/dlPAG) reduces autonomic responses evoked from the DMH, leading to the suggestion that neurons in the l/dlPAG may represent a descending relay for DMH-induced increases in HR and MAP.  

The amygdala, the dorsal periaqueductal gray (dPAG), and the medial hypothalamus have long been recognized to be a neural system responsible for the generation and elaboration of unconditioned fear in the brain.  

Both connectivity analyses identified clusters in the midbrain and periaqueductal gray with greater connectivity to the AI during self pain as opposed to other pain.  

Centrally injected benzodiazepine drugs attenuate anxiety in some limbic structures, such as hypothalamus, amygdala and the midbrain periaqueductal gray (PAG).  

Moderate staining occurred in the lateral posterior nucleus of the thalamus, superficial layers of neocortex, periaqueductal gray, substantia nigra, stria terminalis, nucleus accumbens shell and tegmental nucleus.  

The primary brain structures involved in the expression of rage behavior include the hypothalamus and midbrain periaqueductal gray.  

In particular, as both mGlu and cannabinoid receptors have been found in the periaqueductal gray (PAG), a crucial station in the pain modulatory system, these receptors could be a substrate for producing analgesia at this level.  

OBJECTIVE: To investigate the antinociceptive effect of periaqueductal gray (PAG) administration of herpes simplex virus type-1(HSV-I) amplicon vector-mediated human preproenkephalin gene (HPPE).  

Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences.  

5-HT(1A) modulation within the midbrain periaqueductal gray (PAG) is closely associated with anxiety- or panic-like behavior. However, no effects on c-Fos-ir were detected in the caudal lateral periaqueductal gray (lPAG) and ventrolateral periaqueductal gray (vlPAG) in both the AB and CB groups, and in the dorsolateral periaqueductal gray (dlPAG) of the CB group. Interestingly, c-Fos-ir cells in the dorsomedial periaqueductal gray (dmPAG) column were reduced consistently in both the rostral and caudal PAG in both AB and CB groups.  

Electrical or glutamate stimulation of the dorsal periaqueductal gray matter (DPAG) of rats induces overt defensive behavior, such as freezing or flight, and hyponociception, while glycine and D-serine, a specific NMDA/GLY(B)-site ligand, produced only subtle defensive behavior related to risk assessment and avoidance from the open arms in the elevated plus-maze test.  

In the brainstem, Oxt-ir fibers were found in the periaqueductal gray, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract, and nucleus ambiguus.  

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) and one of its target structures, the ventromedial hypothalamus (VMH), produces a typical behaviour in rats consisting of vigorous running and jumping which is known as "escape behaviour".  

Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures.  

The ventrolateral orbital cortex (VLO) is a component of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway relaying in the periaqueductal gray matter (PAG).  

Researchers are beginning to identify brain sites associated with conditioned contextual fear such as the ventral anterior olfactory nucleus, dorsal premammillary nucleus, ventrolateral periaqueductal gray, cuneiform nucleus, and locus coeruleus.  

The midbrain tectum structures, dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), are involved in the organization of fear and anxiety states during the exposure to dangerous stimuli.  

Evidence from animal models of anxiety has led to the hypothesis that serotonin enhances inhibitory avoidance (related to anxiety) in the forebrain, but inhibits one-way escape (panic) in the midbrain periaqueductal gray (PAG).  

Consistent with previous fMRI studies of pain empathy with adults, the perception of other people in pain in children was associated with increased hemodynamic activity in the neural circuits involved in the processing of first-hand experience of pain, including the insula, somatosensory cortex, anterior midcingulate cortex, periaqueductal gray, and supplementary motor area.  

NPR-C immunoreactivity was detected in several regions, including the periaqueductal gray, oculomotor nucleus, red nucleus and trochlear nucleus of the midbrain; the pontine nucleus, dorsal tegmental nucleus, vestibular nucleus, locus coeruleus, trigeminal motor nucleus, nucleus of the trapezoid body, abducens nucleus and facial nucleus of the pons; and the dorsal motor nucleus of the vagus, hypoglossal nucleus, lateral reticular nucleus, nucleus ambiguus and inferior olivary nucleus of the medulla oblongata.  

This is in line with results of earlier experiments, in which metamizol or LASA were given intravenously or microinjected into the periaqueductal gray matter.  

The periaqueductal gray (PAG) is critically involved in the micturition reflex, but little is known about the neuronal mechanisms involved.  

Significant decreases in rCBF were seen in the thalamus, parabrachial nucleus, periaqueductal gray, hypothalamus and pons.  

The inferior colliculus (IC) together with the dorsal periaqueductal gray (dPAG), the amygdala and the medial hypothalamus make part of the brain aversion system, which has mainly been related to the organization of unconditioned fear.  

Our combined HRV-fMRI approach demonstrated HF correlation with fMRI activity in the hypothalamus, cerebellum, parabrachial nucleus/locus ceruleus, periaqueductal gray, amygdala, hippocampus, thalamus, and dorsomedial/dorsolateral prefrontal, posterior insular, and middle temporal cortices.  

Oxytocin (OT) is one of many neurochemicals released intracerebrally while mothers interact with infants, and we investigated whether OT receptor activity in the ventrocaudal periaqueductal gray (cPAGv) contributes to mothers' reduced anxiety.  

The expression of c-Fos in the pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preoptic nucleus (MPA) regions was increased by the induction of stress urinary incontinence, and acupuncture at the SP6 acupoint significantly decreased c-Fos expression in these areas.  

This effect was likely caused by naloxone blocking conditioned responses in a pain-inhibitory circuit involving opioid-rich areas such as the rostral anterior cingulate cortex, amygdala, and periaqueductal gray.  

Although no significant activation was found over periaqueductal gray (PAG), further analysis showed the mean and maximal signal changes were different under three EA manipulations.  

The effects of 5,6-EET, 8,9-EET, 11,12-EET, and 14,15-EET microinjected into the ventrolateral periaqueductal gray (vlPAG) on the thermally produced tail-flick response were studied in male Sprague-Dawley rats.  

Increased axial diffusivity in CCHS appeared within the lateral medulla and clusters with injury extended from the dorsal midbrain through the periaqueductal gray, raphé, and superior cerebellar decussation, ventrally to the basal-pons.  

Recent insights have demonstrated a central role for dopaminergic neurotransmission in modulating pain perception and natural analgesia within supraspinal regions, including the basal ganglia, insula, anterior cingulate cortex, thalamus and periaqueductal gray.  

RATIONALE: Serotonin in the dorsal periaqueductal gray (DPAG) through the activation of 5-HT(1A) and 5-HT(2A) receptors inhibits escape, a defensive behavior associated with panic attacks.  

It also activates the dorsolateral column of the periaqueductal gray (dlPAG).  

The dorsolateral periaqueductal gray (dlPAG) is a midbrain structure related to anxiety that contains receptors proposed to interact with CBD such as 5HT1A.  

Here, we characterized their morphology and physiology properties and tested the effect of substance P (Sub-P) on them, since the results of many morphological studies suggest that A7 neurons are densely innervated by Sub-P-releasing terminals from nuclei involved in the descending inhibitory system, such as the lateral hypothalamus and periaqueductal gray area.  

On the other hand, the defensive behaviors and aversive emotions produced by stimulation of the dorsal periaqueductal gray matter (DPAG) have been proposed as a model of panic attacks.  

In contrast, microglia was not activated in supraspinal regions of the CNS, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), primary and secondary somatosensory cortex (S1 and S2), insular cortex (IC), amygdala, hippocampus, periaqueductal gray (PAG) and rostral ventromedial medulla (RVM).  

EM-IR fibers and terminals are found widely distributed in many brain areas, including the different columns of the periaqueductal gray (PAG).  

Similar effects were obtained with GR 82334 infusion into the ventromedial nucleus of the hypothalamus (VMH), to which the MeA projects, and into the rostral dorsolateral periaqueductal gray (PAG), to which the VMH projects, but not into the deep layers of the superior colliculus/deep mesencephalic nucleus (dSC/DpMe), an output of the CeA previously shown to be important for fear-potentiated startle.  

The expression of the 5-HT2A receptor mRNA in the nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and spinal dorsal horn of mono-arthritic rats after a ten-day treatment with tramadol was measured with in situ hybridization.  

Activation of these neurons is transmitted to the periaqueductal gray and rostroventromedial medulla (RVM) (descending pain control system).  

AEA is tonically active in the periaqueductal gray matter, a migraine generator.  

Purinergic P2X receptors have been reported to be present in regions of the midbrain periaqueductal gray (PAG).  

Retrograde labeling from the nPGi was prominent in the bed nucleus of the stria terminalis, paraventricular nucleus (PVN), posterior hypothalamus, precommissural nucleus, deep mesencephalic nucleus, and periaqueductal gray (PAG) of both sexes.  

The periaqueductal gray (PAG) of the mesencephalon has been implicated to be involved in the control of micturition.  

6-hydroxydopamine lesions of the A5-7 groups or ibotenic acid lesions of the ventrolateral periaqueductal gray matter (vlPAG) attenuated antinociceptive responses to noxious thermal stimulation (tail-flick test) by both types of anesthetics.  

The participation of the periaqueductal gray matter (PAG) in TI modulation has previously been described.  

Overall, the present results underscore that other routes, aside from the well-established CeA projections to the periaqueductal gray, may contribute to the acquisition/consolidation of the freezing response associated to a TFC task.  

The midbrain periaqueductal gray (PAG) and its descending projections to the rostral ventromedial medulla (RVM) provides an essential neural circuit for the antinociceptive effects of opiates, and has been implicated in the development of tolerance to morphine.  

Previous research has suggested that the ventrolateral column of the periaqueductal gray (vlPAG) plays a crucial role in triggering a decompensatory response (sympathoinhibition, hypotension, bradycardia) to severe blood loss.  

Nevertheless, animals treated with L-NAME at 200 nmol into the lateral ventricle (LV), basolateral amygdala (BLA), dorsolateral periaqueductal gray (dlPAG) matter, lateral septal nucleus (LSN), but not in the bed nucleus of stria terminalis (BNST), displayed impaired AVOID2 in comparison to the control group.  

Given that the ventrolateral periaqueductal gray (vlPAG) plays a major role in morphine antinociception and tolerance, the effects of DMSO on morphine antinociception mediated by the vlPAG needs to be evaluated.  

Following verum, but not sham, acupuncture there was increased DMN connectivity with pain (anterior cingulate cortex (ACC), periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal formation, middle temporal gyrus) related brain regions.  

This was combined with retrograde transport of cholera toxin subunit B from the dorsolateral/lateral- (DL/L-) or the ventrolateral- (VL-) periaqueductal gray (PAG) in order to map the organization of A- and C-fiber input to spinal-brainstem circuits.  

While 50-kHz playback induced sparse fos-like immunoreactivity in frontal association cortex, nucleus accumbens, thalamic parafascicular and paraventricular nuclei, 22-kHz playback elicited c-fos expression in the perirhinal cortex, amygdalar nuclei and the periaqueductal gray.  

Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus--nitric oxide (NO) acts as a neurotransmitter in the rat dorsolateral periaqueductal gray (dlPAG), a midbrain structure that modulates fear and defensive behavior.  

Lactate increased c-Fos expression in serotonergic neurons located in the ventrolateral part of the dorsal raphe nucleus (DRVL) and ventrolateral periaqueductal gray (VLPAG) of control, but not panic-prone, rats.  

Finally, the DPGi sent efferents to the ventrolateral part of the periaqueductal gray matter known to contain paradoxical sleep-suppressing neurons. Taken together, our original results suggest that the PS-on neurons of the DPGi may have their major role in simultaneous inhibitory control over the wake-promoting neurons and the permissive ventrolateral part of the periaqueductal gray matter as a means of influencing vigilance states and especially PS generation..  

In Mecp2B mice, significantly lower values for cortical area were distributed along the rostrocaudal axis, and there was a reduced length of the olfactory bulb ( approximately 10%) and periaqueductal gray matter ( approximately 16%). In Mecp2J mice, while there was significant reduction in rostrocaudal length of cortex, this parameter was also abnormal in hippocampus ( approximately 10%), periaqueductal gray matter ( approximately 13%), fimbria ( approximately 18%), and anterior commissure ( approximately 10%).  

The genes are differentially expressed in the midbrain periaqueductal gray of 129P3 versus C57BL/6 mice, owing to cis-acting genetic elements.  

According to different properties and distribution patterns of the 5-HT receptor subtypes on neurons, the possible mechanism of 5-HT activation of the VLO-periaqueductal gray (PAG) descending antinociceptive pathway is discussed..  

The cortical activation was distributed over the cingulate, motor, somatosensory, insular, and visual cortices, and the subcortical activation involved the caudate putamen, hippocampus, periaqueductal gray, superior colliculus, thalamus, and hypothalamus.  

The chemokine stromal cell-derived growth factor (SDF)-1alpha/CXCL12, a member of the CXC chemokine family, was tested for its possible effect on the analgesic responses of the cannabinoid receptor agonist aminoalkylindole 4,5-dihydro-2-methyl-4-(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo-[ 3,2,1ij]quinolin-6-one [ (+)-WIN 55,212-2, hereafter WIN 55,212-2] at the level of the periaqueductal gray (PAG), a brain region critical to the processing of pain signals, and a primary site of action of many analgesic compounds.  

By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons.  

To determine the underlying mechanisms, we examined its effects on GABAA receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous firings of rat ventrolateral periaqueductal gray (PAG) neurons, either mechanically dissociated, or in acute brain slices.  

The stimulation at the periaqueductal gray and anterior cingulate cortex with different combinations of electrical parameters showed a comparable inhibition of spinal cord dorsal horns activities in response to the mechanical stimuli.  

RESULTS: Placebo-induced activation of opioid neurotransmission was detected in the anterior cingulate, orbitofrontal and insular cortices, nucleus accumbens, amygdala, and periaqueductal gray matter.  

For instance, the paraventricular thalamic nucleus, the bed nucleus of the stria terminalis and the subfornical organ were highly labelled, as were the periaqueductal gray and the nucleus of the solitary tract.  

Nitric oxide (NO) affects neuronal activity of the midbrain periaqueductal gray (PAG).  

Consistent with this, the neurotransmitter substance P (SP) level in affective brain areas including amygdala, hypothalamus, and periaqueductal gray was significantly increased in CatE-/- mice compared with CatE+/+ mice, indicating that the increased aggressive behavior of CatE-/- mice by isolation housing followed by territorial challenge is mainly because of the enhanced SP/NK-1 receptor signaling system.  

We have previously demonstrated that activation of group I-III mGluRs inhibits GABAergic transmission in the midbrain periaqueductal gray (PAG), a region involved in organizing behavioral responses to threat, stress, and pain.  

One runs from the anterior cingulate cortex via the periaqueductal gray (PAG) into the reticular formation of pons and medulla oblongata, and from there to the phonatory motoneurons.  

The neurons of midbrain periaqueductal gray matter may be involved in the analgesia induced by glucocorticoids..  

The nuclei within the song control circuit receive projections from catecholaminergic cell populations involved in attention, arousal and motivation, including periaqueductal gray (PAG), ventral tegmental area (VTA), locus coeruleus (LoC) and sub coeruleus (SC).  

Progression may be a consequence of the mechanisms that generate the migraine attacks (eg, cortical spreading depression) or it may be a function of the activations generated by the attacks (eg, lesions in the periaqueductal gray area), a hypothesis supported by the increase in lesions with attack frequency.  

When fluoro-gold (FG) was used as a retrograde tracer, we found that FG-labeled neurons in the Hb after the microinjection of FG into the periaqueductal gray expressed both MOR and NR1.  

In the paraventricular nucleus of the hypothalamus (PAH), lateral hypothalamic area (LH), paraventricular nucleus of the thalamus (PVT), periaqueductal gray matter (PAG), bed nucleus of the stria terminalis (BNST), locus coeruleus (LC), lateral parabrachial nucleus (Pbl), the complex of the solitary tract nucleus (NTS) and dorsal motor nucleus of the vagus nerve (DMX), numbers of neurons expressing c-Fos protein were much higher in test than in control experiments.  

In the present study, DOI (1 microg, 2 microg or 5 microg per mice) was directly injected to three brain structures, the hippocampus, the amygdala and the periaqueductal gray matter (PAG).  

RESULTS: In a simple model of normal urine storage, bladder and urethral afferents received in the periaqueductal gray (PAG) are mapped in the insula, forming the basis of sensation; the anterior cingulate gyrus (ACG) provides monitoring and control; the prefrontal cortex makes voiding decisions.  

In contrast, GAD65 mRNA was found in the periaqueductal gray that did not express GAD67 mRNA.  

First, analgesic tolerance was not accompanied by mu opioid receptor desensitization in the periaqueductal gray. Finally, naloxone-precipitated morphine withdrawal did not enhance basal or forskolin-stimulated adenylate cyclase activity in nucleus accumbens, prefrontal cortex, amygdala, bed nucleus of stria terminalis or periaqueductal gray.  

Activation of transient receptor potential vanilloid-1 (TRPV1) channels in the periaqueductal gray (PAG) activates OFF antinociceptive neurons of the rostral ventromedial medulla (RVM).  

Studies on the involvement of 5-HT1-mediated mechanisms in the dorsal periaqueductal gray (dPAG) of animals with past stressful experiences have not been conducted so far.  

Within the mesencephalon cough-related FLI was enhanced at the rostral midline area (p < 0.05), but a decrease was found at its caudal part in the periaqueductal gray (p < 0.02).  

The immobility induced by stimulation of the ventral column of the periaqueductal gray (vPAG) has been considered a quiescence characteristic of the recovery component of defense-recuperative processes. Besides, two types of freezing emerge with the electrical stimulation of the dorsal aspects of the periaqueductal gray (dPAG): the dPAG-evoked freezing and the dPAG post-stimulation freezing. The understanding of how the periaqueductal gray generates and elaborates different types of freezing is of relevance for our better knowledge of distinct types of anxiety such as panic disorder or generalized anxiety disorder..  

Pair-housing for 24 h with an unfamiliar rat following fear conditioning resulted in a suppressed autonomic, but not behavioral, response, with Fos expression in the lateral nucleus of the amygdala and ventrolateral periaqueductal gray.  

Given that neurons in the periaqueductal gray (PAG) contribute to morphine antinociception and tolerance, an understanding of desensitization in PAG neurons is particularly relevant.  

This paired nucleus is located close to the midline, immediately dorsal to the periaqueductal gray matter. The TLC differs from the neighboring nuclei of the superior and inferior colliculi and the periaqueductal gray by its distinct connections and cytoarchitecture.  

Individuals who showed greater activity in regions associated with affective and pain processing (dorsal anterior cingulate cortex, amygdala, periaqueductal gray) during scanner-based social rejection reported feeling greater momentary social distress during their daily social interactions.  

The cardiovascular response to l-glu stimulation of the LH was blocked by pretreatment of the ventrolateral portion of the periaqueductal gray matter (vlPAG) with CoCl2 (1mM/100nL), indicating the existence of a synaptic relay of the hypotensive pathway in that area.  

Following 2 h of drug administration, it showed that olanzapine administration significantly decreased PYY binding densities, predominantly in the posterodorsal part of medial amygdaloid nucleus (52%, p<0.05), dorsal part of medial geniculate nucleus (56%, p<0.05), superficial gray layer of the superior colliculus (53%, p<0.05), parabrachial pigmented nucleus (54%, p<0.05) and periaqueductal gray (50%, p<0.05) compared to controls, while rebound increases of PYY binding densities were observed in most of examined regions 48 h later with only medial geniculate nucleus dorsal showing significant increase compared to controls (118%, p<0.01). Alterations in PYY binding densities in brain regions such as the dorsal part of medial geniculate nucleus, superficial gray layer of superior colliculus, periaqueductal gray and parabrachial pigmented nucleus may represent the specific regions that mediate the clinical effects of antipsychotics via neuropeptide Y system.  

Our experiments show that acute thermal hyperalgesia is blocked in periaqueductal gray with the microOR antagonist CTOP, the NMDA antagonist MK801 and the protein kinase C inhibitor chelerythrine. Therefore, a site of action of systemically administered morphine low dose on acute thermal hyperalgesic response appears to be located at the periaqueductal gray.  

Under conditions that produce physiological responses typical of the defense reaction, electrical stimulation of the dorsal periaqueductal gray (dPAG) was found to double c-Fos immunoreactive serotonergic neurons within the mid-rostrocaudal extent of the B3 group (which comprises the raphe magnus and the lateral paragigantocellular reticular nuclei) in anesthetized rats.  

The dorsal periaqueductal gray (dPAG) is an important vocal center and a crucial structure for the expression of defensive responses.  

MPOA stimulation inhibits spinal cord or trigeminal neuronal responses to noxious stimuli or produces analgesia, yet most of these studies utilized electrical stimulation which antidromically activates periaqueductal gray (PAG) and rostroventromedial medulla (RVM) neurons involved in descending modulation of nociception.  

In this study, we quantitatively investigated the effect of UFP-102 at native NOP receptors of the ventrolateral periaqueductal gray (PAG), a crucial midbrain area involved in pain regulation and enriched with NOP receptors, using blind patch-clamp whole-cell recording technique in rat brain slices.  

Agonist-stimulated [ (35)S]GTPgammaS binding was reduced in the hippocampus, cingulate cortex, periaqueductal gray, and cerebellum after all treatments.  

A lower level of ER-related FLI compared to control animals was detected in the pontine raphe region (p<0.05) and the lateral division of mesencephalic periaqueductal gray (p<0.05).  

It is now clear that these drugs also have central actions that include the modulation of descending control of spinal nociception from the midbrain periaqueductal gray (PAG).  

The three brainstem regions examined included the mid-brain periaqueductal gray (PAG), the medullary nucleus raphe magnus (NRM), and the spinal trigeminal nucleus (STN).  

In contrast, the activation in habenular nuclei and the midbrain periaqueductal gray were markedly decreased in STZ rats.  

Labeled axons from the MnPO were mostly observed within the lateral division of the dorsal raphé nucleus and heavily within the ventrolateral periaqueductal gray.  

To visualize supraspinal projections, fluorogold (FG) was injected into the contralateral ventrolateral periaqueductal gray (vlPAG) 6 days prior to formalin or saline injection into the MF.  

The inhibitory effects of gamma-aminobutyric acid (GABA)ergic neurotransmission in the periaqueductal gray matter (PAG) are mediated, at least partly, by metabotropic GABA(B) receptor subtypes whose cellular and subcellular localization is still unknown.  

Ovine CRF (oCRF) is a nonspecific CRF receptor agonist that produces anxiogenic-like effects when injected locally into the dorsal aspects of the periaqueductal gray (PAG).  

Neurons in the nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, project to medullary nucleus raphe magnus (NRM), which is a key medullary relay for descending pain modulation and is critically involved in opioid-induced analgesia.  

Theoretical solutions include increasing inhibitory descending neurotransmitters using monoamine oxidase inhibitors of subtype A in combination with dextroamphetamine, increasing beta endorphin through enzymology and/or ultrasound stimulation of the periaqueductal gray, developing long duration opioid analgesics using spin label probes of morphine and morphine analogs and destructive interference of nociceptive action potentials by eddy currents generated by a variable magnetic field.  

The amygdala-ventral periaqueductal gray circuit is crucial for the expression of contextual conditioned fear. However, little is known about the neural circuits activated when the stimulation of the dorsal periaqueductal gray (dPAG) is used as unconditioned stimulus (US) in conditioned fear paradigms.  

Fragmentation of PKN was observed by Western blotting in samples collected from the parietal cortex, striatum, septal nucleus, hippocampus, and periaqueductal gray matter.All kaolin-induced rats showed ventricular dilatation. The appearance of PKN fragmentation in periaqueductal gray matter was correlated with the extent of ventricular dilation and spatial learning disability.  

The periaqueductal gray area (PAG) is a mesencephalic area involved in cardiovascular modulation.  

A long-loop pathway involving the arcuate nucleus (ARC), ventrolateral periaqueductal gray, and rostral ventrolateral medulla (rVLM) is involved in sympathoinhibitory cardiovascular EA effects.  

Feline defensive rage, a form of aggressive behavior that occurs in response to a threat can be elicited by electrical stimulation of the medial hypothalamus or midbrain periaqueductal gray (PAG).  

Hypoxia/reoxygenation exposure for 8 weeks resulted in vacuolization in the perikarya and dendrites and markedly impaired c-fos activation response to enforced wakefulness in both noradrenergic locus ceruleus and dopaminergic ventral periaqueductal gray wake neurons.  

In contrast, in high experience animals, egr-1 expression in the POM, BST, and the periaqueductal gray (PAG) was not different than the level of expression in unmated controls.  

The regulator of G-protein signaling, the RGS14 protein, associates with MORs in periaqueductal gray matter (PAG) neurons, and when RGS14 is silenced morphine increased the serine 375 phosphorylation in the C terminus of the MOR, a GRK substrate.  

Glutamatergic neurotransmission in the dorsolateral periaqueductal gray (dlPAG) is related to defensive responses.  

Conversely, postoperative compared with preoperative PET scans revealed significant decreases of [ (11)C]diprenorphine binding in the anterior middle cingulate cortex (aMCC), periaqueductal gray (PAG), prefrontal cortex, and cerebellum.  

Using functional magnetic resonance imaging, we found that as the virtual predator grew closer, brain activity shifted from the ventromedial prefrontal cortex to the periaqueductal gray. Moreover, imminence-driven periaqueductal gray activity correlated with increased subjective degree of dread and decreased confidence of escape.  

We have found that ZI projects mainly to laterally located brain stem structures, whereas the main efferents from the IHy are the reuniens thalamic nucleus, precommissural nucleus, posterior hypothalamic area and dorsolateral periaqueductal gray matter.  

We also showed that the tonic inhibition of locus coeruleus (LC) noradrenergic and dorsal raphe (DRN) serotonergic neurons during sleep is due to a tonic GABAergic inhibition by neurons localized in the dorsal paragigantocellular reticular nucleus (DPGi) and the ventrolateral periaqueductal gray (vlPAG).  

Methods CT was administered intraperitoneally (33.3, 50, 75 mu g/kg), intra-cerebral venticularly (2.4 mu g/kg) or microinjected into periaqueductal gray (PAG, 1.2 mu g/kg).  

RESULTS: We found that a limited number of the mother's brain areas were specifically involved in recognition of the mother's own infant, namely orbitofrontal cortex (OFC), periaqueductal gray, anterior insula, and dorsal and ventrolateral parts of putamen.  

Mice were stereotaxically implanted with microinjection cannulae in the periaqueductal gray (PAG) area of the midbrain.  

It has been shown that facilitation of GABA-mediated neurotransmission in the medial nucleus of the amygdala and the dorsal periaqueductal gray (dPAG) inhibits the escape, but not the inhibitory avoidance response generated in the elevated T-maze test of anxiety (ETM).  

The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively).  

We found that the same group of structures that originally modulate the defensive responses evoked by fear stimuli, including the dorso-medial hypothalamus, the superior and inferior colliculus and the dorsal periaqueductal gray, were most labeled following diazepam withdrawal.  

36) reduced oxytocin concentration in the hypothalamic supraoptic nucleus, and elevated oxytocin concentration in the hypothalamic suprachiasmatic nucleus, hypothalamic ventromedial nucleus, thalamic ventral nucleus, periaqueductal gray, raphe magnus nucleus, caudate nucleus, thoracic spinal cord and lumbar spinal cord, but did not alter oxytocin concentration in the hypothalamic paraventricular nucleus, anterior pituitary, posterior pituitary and plasma.  

Physiological studies have demonstrated that the predominant response to EA is excitation in the ARC and that excitatory projections from the ARC to the ventrolateral periaqueductal gray during EA at P5-P6 contribute to inhibition of sympathoexcitatory cardiovascular reflexes.  

Our immunohistochemistry suggested ASIC1a is expressed in the bed nucleus of the stria terminalis, medial amygdala, and periaqueductal gray, which are thought to play important roles in the generation and expression of innate fear. In addition, loss of ASIC1a altered TMT-evoked c-fos expression in the medial amydala and dorsal periaqueductal gray.  

This experiment resulted in strong expression of c-Fos immunoreactivity in the ventrolateral to lateral subdivision throughout the periaqueductal gray (PAG) compared to the non-AP and sham cases.  

T(1) relaxation times were determined for cortex, corpus callosum, caudate putamen, hippocampus, periaqueductal gray, lateral ventricle, and cerebellum and varied from 1651 +/- 28 to 2449 +/- 150 ms at 9.4 T and 1824 +/- 101 to 2772 +/- 235 ms at 17.6 T.  

From the perspective of comparative morphology, the distribution of non-monoaminergic neurons in the common marmoset (Callithrix jacchus) was investigated using an immunohistochemical method with specific antibodies to tyrosine hydroxylase (TH) and aromatic-L-amino acid decarboxylase (AADC).TH-immunoreactive (IR) neurons (but not AADC-IR) neurons were observed in the olfactory tubercle, preoptic suprachiasmatic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, paraventricular nucleus, periaqueductal gray matter, medial longitudinal fasciculus, substantia nigra, and nucleus solitaris.In contrast, AADC-IR (but not TH-IR), small, oval and spindle-shaped neurons were sparsely distributed in the following areas: the hypothalamus from the anterior nucleus to the lateral nucleus, the dorsomedial nucleus, the dorsomedial area of the medial mammillary nucleus and the arcuate nucleus; the midbrain, including the stria medullaris and substantia nigra; and the medulla oblongata, including the dorsal area of the nucleus solitaris and the medullary reticular nucleus.  

The present study evaluated the role of ventrolateral periaqueductal gray (vlPAG)-located orphanin-FQ (OFQ) in the opioid tolerance induced by repeated microinjections of morphine (MOR) into vlPAG.  

A secondary analysis was performed to account for the changes in regional cerebral blood flow at six regions of interest (thalamus, red nucleus, insula, periaqueductal gray, retrosplenial cingular gyri, and the inferior temporal region).  

Repeated IS induces DeltaFosB in the ventrolateral periaqueductal gray (vlPAG), and levels of the protein are highly predictive of an individual's subsequent behavorial deficit-with the strongest DeltaFosB induction observed in the most resilient animals.  

High density of NOP receptor has been found in the ventrolateral periaqueductal gray (vlPAG), the main output pathway involved in descending pain-control system.  

The purpose of this study was to determine the role of prostaglandin E(2) (PGE(2)) in modulating neuronal activity of the dorsolateral periaqueductal gray (dl-PAG) through excitatory and inhibitory synaptic inputs.  

Morphine and delta9-tetrahydrocannabinol (THC) produce antinociception via mu opioid and cannabinoid CB1 receptors, respectively, located in central nervous system (CNS) regions including periaqueductal gray and spinal cord. The present study assessed receptor-mediated G-protein activity in spinal cord and periaqueductal gray following chronic administration of THC, morphine or low dose combination. Administration of THC attenuated cannabinoid CB1 receptor-stimulated G-protein activity in both periaqueductal gray and spinal cord, and administration of morphine decreased mu opioid receptor-stimulated [ 35S]GTPgammaS binding in spinal cord or periaqueductal gray, depending on route of administration.  


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