Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABA(A) receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor

Author(s)

de Freitas, Renato Leonardo ^{[1, 2]} ; Salgado-Rohner, Carlos Jose ^[1] ; Cecilio Hallak, Jaime Eduardo ^{[3, 4]} ; de Souza Crippa, Jose Alexandre ^{[3, 4]} ; Coimbra, Norberto Cysne ^{[1, 2, 5]}

Affiliation

^[1] Univ Sao Paulo, Lab Neuroanat & Neuropsychobiol, Dept Pharmacol, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Inst Neurocience & Behav INeC, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Neurocience & Behav Sci, Div Psychiat, Ribeirao Preto Med Sch, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Fed Rio Grande do Sul, Natl Inst Sci & Translat Technol Med, BR-90046900 Porto Alegre, RS - Brazil

^[5] Univ Sao Paulo, Ribeirao Preto Med Sch, NAP USP Neurobiol Emot, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY; v. 16, n. 8, p. 1781-1798, SEP 2013.
• Web of Science Citations: 23

Abstract

It has been shown that GABA(A) 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 GABA(A) 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. (AU)

• 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
• 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: 09/17258-5 - Study of the involvement of nitrergic system and of glutamatergic and cannabinoid-mediated neurotransmission from the medial prefrontal cortex in the analgesia induced by elaborated escape reactions evoked by GABAergic blockade in the medial hypothalamus
• Grantee: Renato Leonardo de Freitas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral