CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABA(A) receptor blockade in the dorsomedial division of the ventromedial hypothalamus

Author(s)

dos Anjos-Garcia, Tayllon ; Ullah, Farhad ; Falconi-Sobrinho, Luiz Luciano ; Coimbra, Norberto Cysne

• Document type: Journal article
• Source: Neuropharmacology; v. 113, p. 11-pg., 2017-02-01.

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 GABA(A) receptor blockade with bicuculline (BIC) in the dorsomedial division of the ventromedial hypothalamus (VMHdm). We also aimed to characterise the involvement of endocannabinoids and the CB1 cannabinoid 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 CB1 receptor antagonist AM251, followed by GABA(A) receptor 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 CB1 receptor antagonist AM251 in the VMHdm. Moreover, AM251 potentiates de non-oriented escape induced by bicuculline, effect blocked by pretreatment with the TRPV1 channel antagonist 6-I-CPS. These results indicate that AEA modulates the pro-aversive effects of intra-VMHdm-bicuculline treatment, recruiting CB1 cannabinoid receptors and the TRPV1 channel is involved in the AM251-related potentiation of bicuculline effects on non-oriented escape behaviour. (C) 2016 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 13/10984-8 - Influence of the anterior cingulate cortex and involvement of hypothalamic NMDA and AMPA/kainite glutamatergic receptorsin the organization of the defensive behaviorand innate fear-induced antinociception elaborated by posterior hypothalamus
• Grantee: Luiz Luciano Falconi Sobrinho
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 09/54014-7 - Acquisition of a biophotonic imaging system and a multiphoton microscopy system for in vivo imaging
• Grantee: Enilza Maria Espreafico
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 12/03798-0 - Involvement of opioid and endocanabinoid receptors of the substantia nigra on the activity of Nigro-Tectal GABAergic pathways during defensive behaviour elicited by rodents confronted with venomous snakes
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants
• FAPESP's process: 07/01174-1 - Study of the Involvement of opioid-, serotonergic- and noradrenergic-mechanisms of the pain endogenous inhibitory system in antinociceptive processes induced by oriented escape reactions evoked by chemical stimulation of the merdial hypothalamus
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants