PMID- 23521775 OWN - NLM STAT- MEDLINE DCOM- 20140314 LR - 20161125 IS - 1469-5111 (Electronic) IS - 1461-1457 (Linking) VI - 16 IP - 8 DP - 2013 Sep TI - Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor. PG - 1781-98 LID - 10.1017/S1461145713000163 [doi] AB - It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline. FAU - Freitas, Renato Leonardo de AU - Freitas RL AD - Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirao Preto Medical School of the University of Sao Paulo, Av. dos Bandeirantes 3900, Ribeirao Preto, SP, Brazil. FAU - Salgado-Rohner, Carlos Jose AU - Salgado-Rohner CJ FAU - Hallak, Jaime Eduardo Cecilio AU - Hallak JE FAU - Crippa, Jose Alexandre de Souza AU - Crippa JA FAU - Coimbra, Norberto Cysne AU - Coimbra NC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130325 PL - England TA - Int J Neuropsychopharmacol JT - The international journal of neuropsychopharmacology JID - 9815893 RN - 0 (GABA Antagonists) RN - 0 (Piperidines) RN - 0 (Pyrazoles) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (Receptors, GABA-A) RN - 3I4FA44MAI (AM 251) RN - Y37615DVKC (Bicuculline) SB - IM MH - Analysis of Variance MH - Animals MH - Bicuculline/pharmacology/therapeutic use MH - *Defense Mechanisms MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - GABA Antagonists/pharmacology/therapeutic use MH - Hyperalgesia/drug therapy/pathology MH - Hypothalamus/*drug effects/physiology MH - Instinct MH - Male MH - Microinjections MH - Pain Measurement/*drug effects MH - Pain Threshold/drug effects MH - Panic/*drug effects MH - Piperidines/pharmacology MH - Prefrontal Cortex/drug effects/*physiopathology MH - Pyrazoles/pharmacology MH - Rats MH - Rats, Wistar MH - Receptor, Cannabinoid, CB1/antagonists & inhibitors/*metabolism MH - Receptors, GABA-A/*metabolism EDAT- 2013/03/26 06:00 MHDA- 2014/03/15 06:00 CRDT- 2013/03/26 06:00 PHST- 2013/03/26 06:00 [entrez] PHST- 2013/03/26 06:00 [pubmed] PHST- 2014/03/15 06:00 [medline] AID - S1461145713000163 [pii] AID - 10.1017/S1461145713000163 [doi] PST - ppublish SO - Int J Neuropsychopharmacol. 2013 Sep;16(8):1781-98. doi: 10.1017/S1461145713000163. Epub 2013 Mar 25.