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Pascal Carrive - One of the best experts on this subject based on the ideXlab platform.
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role of ventrolateral Periaqueductal Gray neurons in the behavioral and cardiovascular responses to contextual conditioned fear and poststress recovery
Neuroscience, 2003Co-Authors: Peter Walker, Pascal CarriveAbstract:Abstract We have previously shown that conditioned fear to context increases Fos expression in the caudal ventrolateral region of the Periaqueductal Gray in the rat. To understand the reason for this activation and its role in the expression of the contextual fear response, the ventrolateral Periaqueductal Gray was temporarily blocked with bilateral microinjections (0.4 μl) of the GABA agonist muscimol (0.2 mM) or the glutamate antagonist kynurenic acid (0.1 M). Cardiovascular changes and activity were recorded by radio-telemetry and the microinjections were made immediately before testing the conditioned response in the aversive context. Muscimol and kynurenic acid had the same effects: when compared to saline controls, freezing immobility and ultrasonic vocalizations were reduced and replaced by marked locomotor activity, and the increase in heart rate was enhanced; however, the increase in arterial blood pressure remained the same. Interesting changes were also observed when animals were returned to the safe context of their home box after fear (recovery). Basically, the recovery response was either prevented or delayed: instead of returning to resting immobility, the rats remained agitated in their home box with a moderately elevated activity, heart rate and blood pressure. However, the effect of ventrolateral Periaqueductal Gray blockade on heart rate, arterial pressure and activity did not appear to be specific to the fear response or its recovery because they were also observed in animals returned to the safe context of their home box immediately after injection. The later response was also a recovery response from the milder stress of handling and the injection procedure. We discuss the results by arguing that the ventrolateral Periaqueductal Gray is involved in the immobility component of both the fear response and poststress recovery responses. To explain our interpretation we consider the findings in relation to the classic descending defence-arousal system and the hyporeactive-hypotensive immobility pattern that has been attributed to the ventrolateral Periaqueductal Gray. We propose that there is a dual activation of the defence-arousal system and of the ventrolateral Periaqueductal Gray during fear, with the ventrolateral Periaqueductal Gray acting as a brake on the defence-arousal system. The role of this brake is to impose immobility and hold off active defence responses such as fight and flight. The result of this combination of arousal and immobility is a hyperreactive freezing immobility associated with ultrasonic vocalizations, and a pressor response accompanied with a slow rise in heart rate. Basically, the animal is tense and ready for action but temporarily immobilised. The ventrolateral Periaqueductal Gray also acts to impose immobility during recovery; however, this is without coactivation of the defence-arousal system. The result is a return to resting immobility, associated with a return to baseline blood pressure and heart rate. This is an active process that insures a faster and complete return to rest. We conclude that the ventrolateral Periaqueductal Gray is an immobility center involved not only in the fear response but also in poststress recovery responses.
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Lidocaine blockade of amygdala output in fear-conditioned rats reduces Fos expression in the ventrolateral Periaqueductal Gray
Neuroscience, 2000Co-Authors: Pascal Carrive, J LeeAbstract:Abstract We showed recently that conditioned fear to context induces Fos expression in the ventrolateral Periaqueductal Gray [ Neuroscience (1997) 78, 165–177]. Neurons in this region are thought to play an important role in the expression of freezing during conditioned fear. To test the possibility that this activation comes directly from the amygdala, we looked at changes in Fos expression after a unilateral blockade of the ventral amygdalofugal pathway with lidocaine. The pathway contains fibres originating from the central nucleus of the amygdala that project directly and mainly ipsilaterally to the ventrolateral Periaqueductal Gray. Conditioned fear was evoked by re-exposing rats to the same box in which they had previously received electric footshocks. The test re-exposure was preceded by a unilateral microinjection of lidocaine (2%, 0.5–1 μl; n =20) or saline ( n =14). Lidocaine was also tested in non-conditioned animals ( n =13). The results show that, when lidocaine was microinjected in the medial part of the central nucleus of the amygdala or along the ventral amygdalofugal pathway of conditioned rats, fear-induced Fos expression in the ventrolateral Periaqueductal Gray was reduced on the side ipsilateral to the injection (up to 37% reduction in comparison to the contralateral side). Ipsilateral reductions were also observed with saline, but they were weaker (maximum of 27% reduction). Fos expression remained low on both sides in the non-fear-conditioned animals injected with lidocaine. Finally, although freezing was only partly reduced in the conditioned animals unilaterally injected with lidocaine, it was significantly correlated to the ipsilateral reduction in Fos expression. This study provides direct evidence that the projection from the central nucleus of the amygdala to the ventrolateral Periaqueductal Gray is activated during fear and that it contributes to the Fos response of the ventrolateral Periaqueductal Gray.
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the Periaqueductal Gray and defensive behavior functional representation and neuronal organization
Behavioural Brain Research, 1993Co-Authors: Pascal CarriveAbstract:Abstract Recent findings suggest that the Periaqueductal Gray (PAG) can be subdivided on the basis of its anatomical connections and functional representation of cardiovascular and behavioral functions. This new scheme of subdivision postulates the existence of 4 major longitudinal columns located dorsomedial, dorsolateral, lateral and ventrolateral to the aqueduct. Attention has focussed on the lateral and ventrolateral columns, because they contain topographically distinct groups of neurons whose activation results in different forms of defensive or protective reactions. Reactions evoked from the lateral PAG column are associated with somatomotor and autonomic activation and are characteristic of an organism's response to superficial or cutaneous noxious stimuli, whereas reactions evoked from the ventrolateral PAG column are associated with somatomotor and autonomic inhibition and appear to correspond to an organism's response to deep or visceral noxious stimuli. Furthermore, the neurons of these two columns possess some degree of somatotopic and viscerotopic organization and send axon collaterals to multiple targets in the medulla. This model of PAG neuronal organization outlines the basic architectural features of a network involved in the coordinated expression of certain types of defensive/protective reactions.
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Emerging Principles of Organization of the Midbrain Periaqueductal Gray Matter
The Midbrain Periaqueductal Gray Matter, 1991Co-Authors: Richard Bandler, Pascal Carrive, Antoine DepaulisAbstract:Throughout this book the term Periaqueductal Gray (PAG) has been used in preference to the term central Gray, since PAG refers specifically to the portion of the ventricular Gray matter which surrounds the midbrain aqueduct. Rostrally, the PAG is continuous with the periventricular Gray matter surrounding the third ventricle in the hypothalamus and thalamus. Caudally, it is continuous with the periventricular Gray matter which in the dorsal pons forms the ventral and ventrolateral border of the fourth ventricle. Although the oculomotor related group of nuclei (i.e., oculomotor and trochlear nuclei, the Edinger-Westphal nucleus, the nucleus of Darkschewitsch and the interstitial nucleus of Cajal) and the dorsal raphe nucleus, constitute the major part of the Gray matter ventral to the midbrain aqueduct, they are usually considered, on functional and anatomical grounds, separable from the PAG. The midbrain tegmentum laterally adjacent to the PAG has also usually been considered to be a separate entity. However, as discussed by Holstege (this volume), the PAG and the laterally adjacent tegmentum together, likely form a common neuronal pool which is divided by the fiber stream formed by the tectobulbospinal fibers and the fibers of the mesencephalic trigeminal tract.
Hélio Zangrossi - One of the best experts on this subject based on the ideXlab platform.
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nitric oxide in the dorsal Periaqueductal Gray mediates the panic like escape response evoked by exposure to hypoxia
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2019Co-Authors: Gabriel Gripp Fernandes, Ailton Spiacci, Alana Tercino Frias, Lucas C Pinheiro, Jose E Tanussantos, Hélio ZangrossiAbstract:Abstract Exposure of rats to an environment with low O2 levels evokes a panic-like escape behavior and recruits the dorsal Periaqueductal Gray (dPAG), which is considered to be a key region in the pathophysiology of panic disorder. The neurochemical basis of this response is, however, currently unknown. We here investigated the role played by nitric oxide (NO) within the dPAG in mediation of the escape reaction induced by hypoxia exposure. The results showed that exposure of male Wistar rats to 7% O2 increased nitrite levels, a NO metabolite, in the dPAG but not in the amygdala or hypothalamus. Nitrite levels in the dPAG were correlated with the number of escape attempts during the hypoxia challenge. Injections of the NO synthesis inhibitor NPA, the NO-scavenger c- PTIO, or the NMDA receptor antagonist AP-7 into the dorsolateral column of the Periaqueductal Gray (dlPAG) inhibited escape expression during hypoxia, without affecting the rats' locomotion. Intra-dlPAG administration of c-PTIO had no effect on the escape response evoked by the elevated-T maze, a defensive behavior that has also been associated with panic attacks. Altogether, our results suggest that NO plays a critical role in mediation of the panic-like defensive response evoked by exposure to low O2 concentrations.
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nitric oxide in the dorsal Periaqueductal Gray mediates the panic like escape response evoked by exposure to hypoxia
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2019Co-Authors: Gabriel Gripp Fernandes, Ailton Spiacci, Alana Tercino Frias, Lucas C Pinheiro, Jose E Tanussantos, Hélio ZangrossiAbstract:Abstract Exposure of rats to an environment with low O2 levels evokes a panic-like escape behavior and recruits the dorsal Periaqueductal Gray (dPAG), which is considered to be a key region in the pathophysiology of panic disorder. The neurochemical basis of this response is, however, currently unknown. We here investigated the role played by nitric oxide (NO) within the dPAG in mediation of the escape reaction induced by hypoxia exposure. The results showed that exposure of male Wistar rats to 7% O2 increased nitrite levels, a NO metabolite, in the dPAG but not in the amygdala or hypothalamus. Nitrite levels in the dPAG were correlated with the number of escape attempts during the hypoxia challenge. Injections of the NO synthesis inhibitor NPA, the NO-scavenger c- PTIO, or the NMDA receptor antagonist AP-7 into the dorsolateral column of the Periaqueductal Gray (dlPAG) inhibited escape expression during hypoxia, without affecting the rats' locomotion. Intra-dlPAG administration of c-PTIO had no effect on the escape response evoked by the elevated-T maze, a defensive behavior that has also been associated with panic attacks. Altogether, our results suggest that NO plays a critical role in mediation of the panic-like defensive response evoked by exposure to low O2 concentrations.
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a serotonergic deficit in the dorsal Periaqueductal Gray matter may underpin enhanced panic like behavior in diabetic rats
Behavioural Pharmacology, 2017Co-Authors: Eder Gambeta, Hélio Zangrossi, Caio Cesar Sestile, Manoela V Fogaca, Francisco Silveira Guimaraes, Elisabeth Aparecida Audi, Joice Maria Da Cunha, Paula Shimene De Melo Yamashita, Janaina Menezes ZanoveliAbstract:It is known that diabetic (DBT) animals present dysregulation on the serotonergic system in several brain areas associated with anxiety-like responses. The aim of this study was to investigate the involvement of 5-HT1A receptors on dorsal Periaqueductal Gray (dPAG) in the behavioral response related
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involvement of serotonin mediated neurotransmission in the dorsal Periaqueductal Gray matter on cannabidiol chronic effects in panic like responses in rats
Psychopharmacology, 2013Co-Authors: Alline C Campos, Hélio Zangrossi, Marcus Lira Brandao, Vanessa De Paula Soares, Milene C Carvalho, Frederico Rogerio Ferreira, Maria Adrielle Vicente, Antonio Waldo Zuardi, Francisco Silveira GuimaraesAbstract:Rationale Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal Periaqueductal Gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.
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serotonin 2a receptor regulation of panic like behavior in the rat dorsal Periaqueductal Gray matter the role of gaba
Psychopharmacology, 2011Co-Authors: Thatiane De Oliveira Sergio, Valquiria Camin De Bortoli, Hélio ZangrossiAbstract:Rationale Electrical stimulation of the dorsal Periaqueductal Gray (dPAG) evokes escape, a defensive response associated with panic attacks. Stimulation of 5-HT1A or 5-HT2A receptors in this midbrain area equally inhibits escape performance, even though at the molecular level these receptors cause opposite effects, i.e., activation of the former hyperpolarizes the cell membrane, while the latter excites it. A proposal has been made that 5-HT2A receptor agonists exert their inhibitory effect on escape by activating GABAergic interneurons located in the dPAG.
Tor D Wager - One of the best experts on this subject based on the ideXlab platform.
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functional involvement of human Periaqueductal Gray and other midbrain nuclei in cognitive control
The Journal of Neuroscience, 2019Co-Authors: Philip A Kragel, Marta Bianciardi, Ludger Hartley, Gordon Matthewson, Jikyung Choi, Karen S Quigley, Lawrence L Wald, Tor D Wager, Lisa Feldman BarrettAbstract:Recent theoretical advances have motivated the hypothesis that the Periaqueductal Gray (PAG) participates in behaviors that involve changes in the autonomic control of visceromotor activity, including during cognitively demanding tasks. We used ultra-high-field (7 tesla) fMRI to measure human brain activity at 1.1 mm resolution while participants completed a working memory task. Consistent with prior work, participants were less accurate and responded more slowly with increasing memory load—signs of increasing task difficulty. Whole-brain fMRI analysis revealed increased activity in multiple cortical areas with increasing working memory load, including frontal and parietal cortex, dorsal cingulate, supplementary motor area, and anterior insula. Several dopamine-rich midbrain nuclei, such as the substantia nigra and ventral tegmental area, also exhibited load-dependent increases in activation. To investigate PAG involvement during cognitive engagement, we developed an automated method for segmenting and spatially normalizing the PAG. Analyses using cross-validated linear support vector machines showed that the PAG discriminated high versus low working memory load conditions with 95% accuracy in individual subjects based on activity increases in lateral and ventrolateral PAG. Effect sizes in the PAG were comparable in magnitude to those in many of the cortical areas. These findings suggest that cognitive control is not only associated with cortical activity in the frontal and parietal lobes, but also with increased activity in the subcortical PAG and other midbrain regions involved in the regulation of autonomic nervous system function. SIGNIFICANCE STATEMENT Functional neuroimaging in humans has shown that cognitive control engages multiple corticostriatal networks and brainstem nuclei, but theoretical advances suggest that the Periaqueductal Gray (PAG) should also be engaged during cognitively demanding tasks. Recent advances in ultra-high-field fMRI provided an opportunity to obtain the first evidence that increased activation of intermediate and rostral portions of lateral and ventrolateral PAG columns in humans is modulated by cognitive load. These findings suggest that cognitive control is not solely mediated by activity in the cortex, but that midbrain structures important for autonomic regulation also play a crucial role in higher-order cognition.
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common representation of pain and negative emotion in the midbrain Periaqueductal Gray
Social Science Research Network, 2016Co-Authors: Jason T Buhle, Hedy Kober, Kevin N Ochsner, Peter Mendesiedlecki, Jochen Weber, Brent L Hughes, Ethan Kross, Lauren Y Atlas, Kateri Mcrae, Tor D WagerAbstract:Human neuroimaging offers a powerful way to connect animal and human research on emotion, with profound implications for psychological science. However, the gulf between animal and human studies remains a formidable obstacle: human studies typically focus on the cortex and a few subcortical regions such as the amygdala, whereas deeper structures such as the brainstem Periaqueductal Gray (PAG) play a key role in animal models. Here, we directly assessed the role of PAG in human affect by interleaving in a single fMRI session two conditions known to elicit strong emotional responses--physical pain and negative image viewing. Negative affect and PAG activity increased in both conditions. We next examined eight independent data sets, half featuring pain stimulation and half negative image viewing. In sum, these data sets comprised 198 additional participants. We found increased activity in PAG in all eight studies. Taken together, these findings suggest PAG is a key component of human affective responses.
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representation of aversive prediction errors in the human Periaqueductal Gray
Nature Neuroscience, 2014Co-Authors: Mathieu Roy, Daphna Shohamy, Nathaniel D Daw, Marieke Jepma, Elliott G Wimmer, Tor D WagerAbstract:Pain is a primary driver of learning and motivated action. It is also a target of learning, as nociceptive brain responses are shaped by learning processes. We combined an instrumental pain avoidance task with an axiomatic approach to assessing fMRI signals related to prediction errors (PEs), which drive reinforcement-based learning. We found that pain PEs were encoded in the Periaqueductal Gray (PAG), a structure important for pain control and learning in animal models. Axiomatic tests combined with dynamic causal modeling suggested that ventromedial prefrontal cortex, supported by putamen, provides an expected value-related input to the PAG, which then conveys PE signals to prefrontal regions important for behavioral regulation, including orbitofrontal, anterior mid-cingulate and dorsomedial prefrontal cortices. Thus, pain-related learning involves distinct neural circuitry, with implications for behavior and pain dynamics.
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identification of discrete functional subregions of the human Periaqueductal Gray
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Ajay B Satpute, Marta Bianciardi, Jikyung Choi, Lawrence L Wald, Tor D Wager, Lisa Feldman Barrett, Jason T Buhle, Julien CohenadadAbstract:The midbrain Periaqueductal Gray (PAG) region is organized into distinct subregions that coordinate survival-related responses during threat and stress [Bandler R, Keay KA, Floyd N, Price J (2000) Brain Res 53 (1):95–104]. To examine PAG function in humans, researchers have relied primarily on functional MRI (fMRI), but technological and methodological limitations have prevented researchers from localizing responses to different PAG subregions. We used high-field strength (7-T) fMRI techniques to image the PAG at high resolution (0.75 mm isotropic), which was critical for dissociating the PAG from the greater signal variability in the aqueduct. Activation while participants were exposed to emotionally aversive images segregated into subregions of the PAG along both dorsal/ventral and rostral/caudal axes. In the rostral PAG, activity was localized to lateral and dorsomedial subregions. In caudal PAG, activity was localized to the ventrolateral region. This shifting pattern of activity from dorsal to ventral PAG along the rostrocaudal axis mirrors structural and functional neurobiological observations in nonhuman animals. Activity in lateral and ventrolateral subregions also grouped with distinct emotional experiences (e.g., anger and sadness) in a factor analysis, suggesting that each subregion participates in distinct functional circuitry. This study establishes the use of high-field strength fMRI as a promising technique for revealing the functional architecture of the PAG. The techniques developed here also may be extended to investigate the functional roles of other brainstem nuclei.
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common representation of pain and negative emotion in the midbrain Periaqueductal Gray
Social Cognitive and Affective Neuroscience, 2013Co-Authors: Jason T Buhle, Hedy Kober, Kevin N Ochsner, Peter Mendesiedlecki, Jochen Weber, Brent L Hughes, Ethan Kross, Lauren Y Atlas, Kateri Mcrae, Tor D WagerAbstract:Human neuroimaging offers a powerful way to connect animal and human research on emotion, with profound implications for psychological science. However, the gulf between animal and human studies remains a formidable obstacle: human studies typically focus on the cortex and a few subcortical regions such as the amygdala, whereas deeper structures such as the brainstem Periaqueductal Gray (PAG) play a key role in animal models. Here, we directly assessed the role of PAG in human affect by interleaving in a single fMRI session two conditions known to elicit strong emotional re
Marcus Lira Brandao - One of the best experts on this subject based on the ideXlab platform.
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involvement of serotonin mediated neurotransmission in the dorsal Periaqueductal Gray matter on cannabidiol chronic effects in panic like responses in rats
Psychopharmacology, 2013Co-Authors: Alline C Campos, Hélio Zangrossi, Marcus Lira Brandao, Vanessa De Paula Soares, Milene C Carvalho, Frederico Rogerio Ferreira, Maria Adrielle Vicente, Antonio Waldo Zuardi, Francisco Silveira GuimaraesAbstract:Rationale Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal Periaqueductal Gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.
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evidence for mediation of nociception by injection of the nk 3 receptor agonist senktide into the dorsal Periaqueductal Gray of rats
Psychopharmacology, 2009Co-Authors: Gabriel Shimizu Bassi, Ana Carolina Broiz, Margarete Z Gomes, Marcus Lira BrandaoAbstract:Rationale Ultrasound vocalizations (USVs) at approximately 22 kHz are usual components of the defensive response of rats. However, depending on the neural substrate that is activated, such as the dorsal Periaqueductal Gray (dPAG), USV emissions may be reduced. Activation of neurokinin-1 (NK-1)-mediated mechanisms of the dPAG causes analgesia, reduced 22 kHz USVs, and anxiogenic-like effects in rats exposed to the elevated plus maze (EPM). Involvement of other types of neurokinin receptors in this activation has not yet been evaluated.
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different patterns of freezing behavior organized in the Periaqueductal Gray of rats association with different types of anxiety
Behavioural Brain Research, 2008Co-Authors: Marcus Lira Brandao, Janaina Menezes Zanoveli, Raquel C Ruizmartinez, Luciana Chrystine Oliveira, J LandeirafernandezAbstract:Freezing defined as the complete absence of body movements is a normal response of animals to unavoidable fear stimuli. The present review presents a series of evidence relating different defensive patterns with specific anxiety disorders. There are at least four different kinds of freezing with specific neural substrates. 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. There is an isomorphism between freezing response to contextual stimuli paired with electrical shocks and generalized anxiety disorder. 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. Evidence is presented in support of the hypothesis that whereas dPAG-evoked freezing would serve as a model of panic attacks, the dPAG post-stimulation freezing appears to be a model of panic disorder. It is also proposed that conditioned freezing plus dPAG electrical stimulation might also mimic panic disorder with agoraphobia. A model of serotoninergic modulation through on- and off-cells of the defense reaction generated in the dPAG is also presented. 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.
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dorsolateral and ventral regions of the Periaqueductal Gray matter are involved in distinct types of fear
Neuroscience & Biobehavioral Reviews, 2001Co-Authors: Daniel Machado Vianna, J Landeirafernandez, Marcus Lira BrandaoAbstract:Stepwise increases in the electrical stimulation of the dorsolateral Periaqueductal Gray (dlPAG) produces alertness, then freezing and finally escape. This paper examines whether this freezing is (i) caused by Pavlovian fear conditioning to the contextual cues present during stimulation and (ii) the result of the stimulation of neurons located inside the dlPAG or elsewhere. To this end, freezing behavior was assessed in rats exposed either to the same or a different environment (context shift test) following the application of either footshocks or stimulation of the dlPAG at the freezing threshold. Rats submitted to footshocks presented freezing to the context 24h later whereas rats submitted to the dlPAG stimulation showed freezing only immediately after the stimulation, regardless of the context. In the second experiment, aversive states generated by activation of the dlPAG were assessed either by measuring the thresholds for freezing and escape responses or the duration of these responses following microinjections of semicarbazide inside the dlPAG. The duration of freezing behavior was also measured in rats submitted to a contextual fear-conditioning paradigm using footshocks as unconditioned stimulus. Lesions of the ventral Periaqueductal Gray (vPAG) disrupted conditioned freezing to contextual cues associated to footshocks but vPAG lesions did not change the threshold of either freezing or escape responses elicited by electrical stimulation of the dlPAG. Lesions of the vPAG did not change the amount of freezing or escape responses produced by microinjections of semicarbazide into the dlPAG. These results indicate that stimulation of dlPAG neurons produce freezing behavior independent of any contextual fear conditioning and add to previously reported evidence showing that the vPAG is a critical structure for the expression of conditioned fear. In contrast, the neural substrate of unconditioned dlPAG stimulation-induced freezing is likely to elaborate unconditioned fear responses to impending danger, which have been implicated in panic disorder.
Francisco Silveira Guimaraes - One of the best experts on this subject based on the ideXlab platform.
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a serotonergic deficit in the dorsal Periaqueductal Gray matter may underpin enhanced panic like behavior in diabetic rats
Behavioural Pharmacology, 2017Co-Authors: Eder Gambeta, Hélio Zangrossi, Caio Cesar Sestile, Manoela V Fogaca, Francisco Silveira Guimaraes, Elisabeth Aparecida Audi, Joice Maria Da Cunha, Paula Shimene De Melo Yamashita, Janaina Menezes ZanoveliAbstract:It is known that diabetic (DBT) animals present dysregulation on the serotonergic system in several brain areas associated with anxiety-like responses. The aim of this study was to investigate the involvement of 5-HT1A receptors on dorsal Periaqueductal Gray (dPAG) in the behavioral response related
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involvement of serotonin mediated neurotransmission in the dorsal Periaqueductal Gray matter on cannabidiol chronic effects in panic like responses in rats
Psychopharmacology, 2013Co-Authors: Alline C Campos, Hélio Zangrossi, Marcus Lira Brandao, Vanessa De Paula Soares, Milene C Carvalho, Frederico Rogerio Ferreira, Maria Adrielle Vicente, Antonio Waldo Zuardi, Francisco Silveira GuimaraesAbstract:Rationale Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that promotes antianxiety and anti-panic effects in animal models after acute systemic or intra-dorsal Periaqueductal Gray (DPAG) administration. However, the effects of CBD repeated administration, and the possible mechanisms involved, in animal models of anxiety- and panic-related responses remain poorly understood.
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activation of cannabinoid cb1 receptors in the dorsolateral Periaqueductal Gray induces anxiolytic effects in rats submitted to the vogel conflict test
European Journal of Pharmacology, 2008Co-Authors: S F Lisboa, Leonardo B M Resstel, Daniele C Aguiar, Francisco Silveira GuimaraesAbstract:Abstract There are contradictory results concerning the effects of systemic injections of cannabinoid agonists in anxiety-induced behavioral changes. Direct drug administration into brain structures related to defensive responses could help to clarify the role of cannabinoids in these changes. Activation of cannabinoid CB 1 receptors in the dorsolateral Periaqueductal Gray induces anxiolytic-like effects in the elevated plus maze. The aim of this work was to verify if facilitation of endocannabinoid-mediated neurotransmission in this region would also produce anxiolytic-like effects in another model of anxiety, the Vogel conflict test. 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. After another 24 h-period of water deprivation, they received the microinjections and, 10 min later, were placed into the experimental box. In this box an electrical shock (0.5 mA, 2 s) was delivered in the spout of a drinking bottle at every twenty licks. The animals received a first microinjection of vehicle (0.2 µl) or AM251 (a cannabinoid CB 1 receptor antagonist; 100 pmol) followed, 5 min later, by a second microinjection of vehicle, anandamide (an endocannabinoid, 5 pmol), AM404 (an inhibitor of anandamide uptake, 50 pmol) or URB597 (an inhibitor of Fatty Acid Amide Hydrolase, 0.01 or 0.1 nmol). Anandamide, AM404 and URB597 (0.01 nmol) increased the total number of punished licks. These effects were prevented by AM251. 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.
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involvement of 5ht1a receptors in the anxiolytic like effects of cannabidiol injected into the dorsolateral Periaqueductal Gray of rats
Psychopharmacology, 2008Co-Authors: Alline C Campos, Francisco Silveira GuimaraesAbstract:Rationale Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa plant that induces anxiolytic effects. However, the brain sites and mechanisms of these effects remain poorly understood. The dorsolateral Periaqueductal Gray (dlPAG) is a midbrain structure related to anxiety that contains receptors proposed to interact with CBD such as 5HT1A. In addition, since CBD has been shown to inhibit anandamide metabolism, CB1 receptors could also be involved in the effects of this cannabinoid.
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activation of cb1 cannabinoid receptors in the dorsolateral Periaqueductal Gray reduces the expression of contextual fear conditioning in rats
Psychopharmacology, 2008Co-Authors: Leonardo B M Resstel, S F Lisboa, Daniele C Aguiar, Fernando M A Correa, Francisco Silveira GuimaraesAbstract:Rationale Conditioned fear to context causes freezing and cardiovascular changes in rodents and has been used to measure anxiety. It also activates the dorsolateral column of the Periaqueductal Gray (dlPAG). Microinjections of cannabinoid agonists into the dlPAG produced anxiolytic-like effects in the elevated plus maze, but the effects of these treatments on fear conditioning remains unknown.
