urb602 and arachidonyl-2-chloroethylamide

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 CB

Topics: Animals; Arachidonic Acids; Benzamides; Biphenyl Compounds; Blood Pressure; Cannabinoids; Carbamates; Corticosterone; Dorsomedial Hypothalamic Nucleus; Endocannabinoids; Indoles; Male; Microinjections; N-Methylaspartate; Panic Disorder; Piperidines; Pyrazoles; Rats