title: Effects of alprazolam and cannabinoid-related compounds in an animal model of panic attack.
abstract: Selective stimulation of carotid chemoreceptors by intravenous infusion of low doses of potassium cyanide (KCN) produces short-lasting escape responses that have been proposed as a model of panic attack. In turn, preclinical studies suggest that facilitation of the endocannabinoid system attenuate panic-like responses. Here, we compared the effects of cannabinoid-related compounds to those of alprazolam, a clinically effective panicolytic, on the duration of the escape reaction induced by intravenous infusion of KCN (80μg) in rats. Alprazolam (1, 2, 4mg/kg) decreased escape duration at doses that did not alter basal locomotor activity. URB597 (0.1, 0.3, 1mg/kg; inhibitor of anandamide hydrolysis), WIN55,212-2 (0.1, 0.3, 1mg/kg; synthetic cannabinoid), arachidonoyl-serotonin (1, 2.5, 5mg/kg; dual TRPV1 and anandamide hydrolysis inhibitor), and cannabidiol (5, 10, 20, 40mg/kg; a phytocannabinoid) did not decrease escape duration. Alprazolam also prevented the increase in arterial pressure evoked by KCN, while bradycardia was unchanged. This study reinforces the validity of the KCN-evoked escape as a model of panic attack. However, it does not support a role for the endocannabinoid system in this behavioral response. These results might have implications for the screening of novel treatments for panic disorder.
authors.affiliation: Graduate School in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Luara A
authors.initials: LA
authors.lastname: Batista
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Andrea S
authors.initials: AS
authors.lastname: Haibara
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo, Brazil.
authors.forename: Luiz C
authors.initials: LC
authors.lastname: Schenberg
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil. Electronic address: fabriciomoreira@icb.ufmg.br.
authors.forename: Fabricio A
authors.initials: FA
authors.lastname: Moreira
mesh_terms: D000525:Alprazolam / Q000627:therapeutic use*; D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D001095:Arachidonic Acids / Q000627:therapeutic use; D001549:Benzamides / Q000627:therapeutic use; D048588:Benzoxazines / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002186:Cannabinoids / Q000627:therapeutic use*; D002219:Carbamates / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000633:toxicity; D004924:Escape Reaction / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009025:Morpholines / Q000627:therapeutic use; D009281:Naphthalenes / Q000627:therapeutic use; D016584:Panic Disorder / Q000139:chemically induced / Q000188:drug therapy*; D011190:Potassium Cyanide / Q000633:toxicity; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D001549:Benzamides; D048588:Benzoxazines; D002186:Cannabinoids; D002219:Carbamates; D004791:Enzyme Inhibitors; D006993:Hypnotics and Sedatives; D009025:Morpholines; D009281:Naphthalenes; C114007:arachidonoylserotonin; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester; D012701:Serotonin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D011190:Potassium Cyanide; D000525:Alprazolam
keywords: Aversion; Benzodiazepines; CB(1) receptor; Cannabinoid; Chemoreflex; Panic