PMID- 27062913 OWN - NLM STAT- MEDLINE DCOM- 20170630 LR - 20180329 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 113 IP - Pt A DP - 2017 Feb TI - CB(1) cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABA(A) receptor blockade in the dorsomedial division of the ventromedial hypothalamus. PG - 156-166 LID - S0028-3908(16)30139-3 [pii] LID - 10.1016/j.neuropharm.2016.04.003 [doi] AB - 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 CB(1) 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 CB(1) 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 CB(1) receptor antagonist AM251 in the VMHdm. Moreover, AM251 potentiates de non-oriented escape induced by bicuculline, effect blocked by pre-treatment with the TRPV(1) channel antagonist 6-I-CPS. These results indicate that AEA modulates the pro-aversive effects of intra-VMHdm-bicuculline treatment, recruiting CB(1) cannabinoid receptors and the TRPV1 channel is involved in the AM251-related potentiation of bicuculline effects on non-oriented escape behaviour. CI - Copyright A(c) 2016 Elsevier Ltd. All rights reserved. FAU - Dos Anjos-Garcia, Tayllon AU - Dos Anjos-Garcia T AD - Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (USP), Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Ullah, Farhad AU - Ullah F AD - Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (USP), Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Falconi-Sobrinho, Luiz Luciano AU - Falconi-Sobrinho LL AD - Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (USP), Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil. FAU - Coimbra, Norberto Cysne AU - Coimbra NC AD - Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo (USP), Av. Bandeirantes 3900, Ribeirao Preto, Sao Paulo, 14049-900, Brazil; NAP-USP-Neurobiology of Emotions (NuPNE) Research Centre, FMRP-USP, Ribeirao Preto, Sao Paulo, Brazil. Electronic address: nccoimbr@fmrp.usp.br. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160408 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Arachidonic Acids) RN - 0 (Endocannabinoids) RN - 0 (GABA-A Receptor Antagonists) RN - 0 (Piperidines) RN - 0 (Polyunsaturated Alkamides) RN - 0 (Pyrazoles) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (Receptors, GABA-A) RN - 0 (TRPV Cation Channels) RN - 0 (Trpv1 protein, rat) RN - 3I4FA44MAI (AM 251) RN - UR5G69TJKH (anandamide) RN - Y37615DVKC (Bicuculline) SB - IM MH - Animals MH - Arachidonic Acids/administration & dosage MH - Bicuculline/administration & dosage MH - Disease Models, Animal MH - Endocannabinoids/administration & dosage MH - Escape Reaction/drug effects/*physiology MH - GABA-A Receptor Antagonists/administration & dosage MH - Male MH - Panic Disorder/chemically induced/physiopathology MH - Piperidines/administration & dosage MH - Polyunsaturated Alkamides/administration & dosage MH - Pyrazoles/administration & dosage MH - Rats MH - Rats, Wistar MH - Receptor, Cannabinoid, CB1/agonists/antagonists & inhibitors/*physiology MH - Receptors, GABA-A/*physiology MH - TRPV Cation Channels/*physiology MH - Ventromedial Hypothalamic Nucleus/drug effects/*physiology OTO - NOTNLM OT - CB(1) cannabinoid receptor OT - Defensive behaviour OT - Endocannabinoid neuromodulators OT - GABA(A) receptor OT - TRPV1 channel OT - Ventromedial hypothalamus EDAT- 2016/11/05 06:00 MHDA- 2017/07/01 06:00 CRDT- 2016/11/05 06:00 PHST- 2015/08/12 00:00 [received] PHST- 2016/03/22 00:00 [revised] PHST- 2016/04/04 00:00 [accepted] PHST- 2016/11/05 06:00 [pubmed] PHST- 2017/07/01 06:00 [medline] PHST- 2016/11/05 06:00 [entrez] AID - S0028-3908(16)30139-3 [pii] AID - 10.1016/j.neuropharm.2016.04.003 [doi] PST - ppublish SO - Neuropharmacology. 2017 Feb;113(Pt A):156-166. doi: 10.1016/j.neuropharm.2016.04.003. Epub 2016 Apr 8.