5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception.
The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.
['Biagioni|Audrey Franceschi|AF|', 'de Oliveira|Rithiele Cristina|RC|', 'de Oliveira|Ricardo|R|', 'da Silva|Juliana Almeida|JA|', 'dos Anjos-Garcia|Tayllon|T|', 'Roncon|Camila Marroni|CM|', 'Corrado|Alexandre Pinto|AP|', 'Zangrossi|Hélio|H|', 'Coimbra|Norberto Cysne|NC|']
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin D000704:Analysis of Variance D000818:Animals D001640:Bicuculline D001710:Biotin D003911:Dextrans D065847:Dorsal Raphe Nucleus D004302:Dorsomedial Hypothalamic Nucleus D004305:Dose-Response Relationship, Drug D004924:Escape Reaction D005239:Fear D058787:GABA-A Receptor Antagonists D008297:Male D008845:Microinjections D009434:Neural Pathways D010147:Pain Measurement D010879:Piperazines D011725:Pyridines D051381:Rats D017208:Rats, Wistar D044282:Receptor, Serotonin, 5-HT1A D012702:Serotonin Antagonists
Dorsomedial hypothalamus Antinociception 5-HT(1A) receptor Biotinylated dextran amine neurotracer Dorsal raphe nucleus outputs Panic-like behaviour