title: 5-HT1A and 5-HT2A receptor control of a panic-like defensive response in the rat dorsomedial hypothalamic nucleus.
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.
authors.affiliation: 1Department of Health Sciences, Federal University of Espírito Santo, CEUNES-UFES, São Mateus, Brazil.
authors.forename: Valquíria Camin
authors.initials: VC
authors.lastname: de Bortoli
authors.forename: Paula Shimene de Melo
authors.initials: PS
authors.lastname: Yamashita
authors.forename: Hélio
authors.initials: H
authors.lastname: Zangrossi
mesh_terms: D000818:Animals; D004302:Dorsomedial Hypothalamic Nucleus / Q000378:metabolism; D004558:Electric Stimulation; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D010200:Panic / Q000502:physiology*; D010487:Periaqueductal Gray / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
chemical_list: D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D007099:Imipramine
keywords: Panic; antidepressants; dorsomedial hypothalamus; escape; imipramine and fluoxetine; serotonin