title: Intra-dorsal periaqueductal gray administration of cannabidiol blocks panic-like response by activating 5-HT1A receptors.
abstract: Activation of 5-HT1A receptors in the dorsal periaqueductal gray (dPAG) impairs escape behavior, suggesting a panicolytic-like effect. Cannabidiol (CBD), a major non-psychotomimetic compound present in Cannabis sativa, causes anxiolytic-like effects after intra-dPAG microinjections by activating 5-HT1A receptors. In the present work we tested the hypothesis that CBD could also impair escape responses evoked by two proposed animal models of panic: the elevated T-maze (ETM) and electric stimulation of dPAG. In experiment 1 male Wistar rats with a single cannula implanted in the dPAG received a microinjection of CBD or vehicle and, 10 min later, were submitted to the ETM and open field tests. In experiment 2 escape electrical threshold was measured in rats with chemitrodes implanted in the dPAG before and 10 min after CBD microinjection. In experiment 3 similar to experiment 2 except that the animals received a previous intra-dPAG administration of WAY-100635, a 5-HT1A receptor antagonist, before CBD treatment. In the ETM microinjection of CBD into the dPAG impaired inhibitory avoidance acquisition, an anxiolytic-like effect, and inhibited escape response, a panicolytic-like effect. The drug also increased escape electrical threshold, an effect that was prevented by WAY-100635. Together, the results suggest that CBD causes panicolytic effects in the dPAG by activating 5-HT1A receptors.
authors.affiliation: Neuroscience and Behavioral Sciences, School of Medicine of Ribeirão Preto, Campus USP, Ribeirão Preto, SP, Brazil. vanpaso@cb.ufrn.br
authors.forename: Vanessa de Paula
authors.initials: Vde P
authors.lastname: Soares
authors.forename: Alline Cristina
authors.initials: AC
authors.lastname: Campos
authors.forename: Valquíria Camin de
authors.initials: VC
authors.lastname: Bortoli
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimarães
authors.forename: Antonio Waldo
authors.initials: AW
authors.lastname: Zuardi
mesh_terms: D000818:Animals; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology*; D004558:Electric Stimulation; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D023421:Models, Animal; D010200:Panic / Q000187:drug effects / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists
chemical_list: D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D002185:Cannabidiol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide