title: CB1cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABAAreceptor blockade in the dorsomedial division of the ventromedial hypothalamus.
abstract: The effects of cannabinoids in brain areas expressing cannabinoid receptors, such as hypothalamic nuclei, are not yet well known. Several studies have demonstrated the role of hypothalamic nuclei in the organisation of behavioural responses induced through innate fear and panic attacks. Panic-prone states are experimentally induced in laboratory animals through a reduction in the GABAergic activity. The aim of the present study was to examine panic-like elaborated defensive behaviour evoked by GABAAreceptor blockade with bicuculline (BIC) in the dorsomedial division of the ventromedial hypothalamus (VMHdm). We also aimed to characterise the involvement of endocannabinoids and the CB1cannabinoid receptor in the modulation of elaborated defence behavioural responses organised with the VMHdm. The guide-cannula was stereotaxicaly implanted in VMHdm and the animals were treated with anandamide (AEA) at different doses, and the effective dose was used after the pre-treatment with the CB1receptor antagonist AM251, followed by GABAAreceptor blockade in VMHdm. The results showed that the intra-hypothalamic administration of AEA at an intermediate dose (5 pmol) attenuated defence responses induced through the intra-VMHdm microinjection of bicuculline (40 ng). This effect, however, was inhibited when applied central microinjection of the CB1receptor antagonist AM251 in the VMHdm. Moreover, AM251 potentiates de non-oriented escape induced by bicuculline, effect blocked by pre-treatment with the TRPV1channel antagonist 6-I-CPS. These results indicate that AEA modulates the pro-aversive effects of intra-VMHdm-bicuculline treatment, recruiting CB1cannabinoid receptors and the TRPV1 channel is involved in the AM251-related potentiation of bicuculline effects on non-oriented escape behaviour.
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors.forename: Tayllon
authors.initials: T
authors.lastname: Dos Anjos-Garcia
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ullah
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
authors.forename: Luiz Luciano
authors.initials: LL
authors.lastname: Falconi-Sobrinho
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil; NAP-USP-Neurobiology of Emotions (NuPNE) Research Centre, FMRP-USP, Ribeirão Preto, São Paulo, Brazil. Electronic address: nccoimbr@fmrp.usp.br.
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage; D001640:Bicuculline / Q000008:administration & dosage; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000008:administration & dosage; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D008297:Male; D016584:Panic Disorder / Q000139:chemically induced / Q000503:physiopathology; D010880:Piperidines / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D058787:GABA-A Receptor Antagonists; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011963:Receptors, GABA-A; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; C103505:AM 251; C078814:anandamide; D001640:Bicuculline
keywords: CB(1) cannabinoid receptor; Defensive behaviour; Endocannabinoid neuromodulators; GABA(A) receptor; TRPV1 channel; Ventromedial hypothalamus