Hypothalamic endocannabinoid signalling modulates aversive responses related to panic attacks

Recurrent panic attacks, comprising emotional and cardiovascular aversive responses, are common features in panic disorder, a subtype of anxiety disorder. The underlying brain circuitry includes nuclei of the hypothalamus, such as the dorsomedial hypothalamus (DMH). The endocannabinoid system has be...

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Bibliographic Details
Published in:	Neuropharmacology Vol. 148; pp. 284 - 290
Main Authors:	Viana, Thércia G., Bastos, Juliana R., Costa, Rayssa B., Hott, Sara C., Mansur, Frederico S., Coimbra, Cândido C., Resstel, Leonardo B., Aguiar, Daniele C., Moreira, Fabrício A.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-04-2019
Subjects:	Animals Arachidonic Acids - pharmacology Benzamides - pharmacology Biphenyl Compounds - antagonists & inhibitors Biphenyl Compounds - pharmacology Blood Pressure - drug effects Cannabinoids - pharmacology Carbamates - pharmacology Corticosterone - blood Dorsomedial Hypothalamic Nucleus - drug effects Dorsomedial Hypothalamic Nucleus - physiopathology Endocannabinoids - physiology Indoles - pharmacology Male Microinjections N-Methylaspartate - antagonists & inhibitors Panic Disorder - chemically induced Panic Disorder - physiopathology Panic Disorder - prevention & control Piperidines - pharmacology Pyrazoles - pharmacology Rats
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Summary:	Recurrent panic attacks, comprising emotional and cardiovascular aversive responses, are common features in panic disorder, a subtype of anxiety disorder. The underlying brain circuitry includes nuclei of the hypothalamus, such as the dorsomedial hypothalamus (DMH). The endocannabinoid system has been proposed to modulate several biological processes in the hypothalamus. Thus, we tested the hypothesis that hypothalamic endocannabinoid signalling controls aversive responses in an animal model of panic attacks. Local infusion of NMDA into the DMH of rats induced panic-like behaviour. This effect was prevented by local, but not intraperitoneal, injection of a 2-arachidonoylglycerol (2-AG) hydrolysis inhibitor (MAGL inhibitor, URB602). The anandamide hydrolysis inhibitor (FAAH inhibitor), URB597, was ineffective. The anti-aversive action of URB602 was reversed by CB1 and CB2 antagonists (AM251 and AM630, respectively), and mimicked by CB1 and CB2 agonists (ACEA and JWH133, respectively). URB602 also prevented the cardiovascular effects of DMH-stimulation in anaesthetised animals. None of the treatments modified blood corticosterone levels. In conclusion, facilitation of 2-AG-signalling in the DMH modulates panic-like responses. The possible mechanisms comprise activation of both CB1 and CB2 receptors in this brain region. •The endocannabinoid 2-AG modulates aversive responses in the hypothalamus.•Local inhibition of 2-AG hydrolysis inhibits panic-like responses.•This effect depends on both CB1 and CB2 receptor activation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0028-3908 1873-7064
DOI:	10.1016/j.neuropharm.2019.01.022