5-HT1A and 5-HT2A receptor control of a panic-like defensive response in the rat dorsomedial hypothalamic nucleus

Author(s)

de Bortoli, Valquiria Camin ; de Melo Yamashita, Paula Shimene ; Zangrossi, Helio, Jr.

• Document type: Journal article
• Source: JOURNAL OF PSYCHOPHARMACOLOGY; v. 27, n. 12, p. 8-pg., 2013-12-01.

Abstract

The dorsomedial nucleus of the hypothalamus (DMH) has long been implicated in the genesis/regulation of escape, a panic-related defensive behavior. In the dorsal periaqueductal gray matter (dPAG), another key panic-associated area, serotonin, through the activation of 5-HT1A and 5-HT2A receptors, exerts an inhibitory role on escape expression. This panicolytic-like effect is facilitated by chronic treatment with clinically effective antipanic drugs such as fluoxetine and imipramine. It is still unclear whether serotonin within the DMH plays a similar regulatory action. The results showed that intra-DMH injection of the 5-HT1A receptor agonist 8-OH-DPAT, the preferential 5-HT2A receptor agonist DOI, but not the 5-HT2C agonist MK-212, inhibited the escape reaction of male Wistar rats evoked by electrical stimulation of the DMH. Local microinjection of the 5-HT1A antagonist WAY-100635 or the preferential 5-HT2A antagonist ketanserin was ineffective. Whereas chronic (21 days) systemic treatment with imipramine potentiated the anti-escape effect of both 8-OH-DPAT and DOI, repeated administration of fluoxetine enhanced the effect of the latter agonist. The results indicate that 5-HT1A and 5-HT2A receptors within the DMH play a phasic inhibitory role upon escape expression, as previously reported in the dPAG. Facilitation of 5-HT-mediated neurotransmission in the DMH may be implicated in the mode of action of antipanic drugs. (AU)

• FAPESP's process: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 08/03123-8 - Role of 5-HT1A and 5-HT2A serotoninergic receptors of the dorsomedial nucleus of the hypothalamus in the mediation of defensive behaviors related to panic
• Grantee: Valquíria Camin de Bortoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral