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5-Hydroxytryptamine 2A receptors of the dorsal raphe nucleus modulate panic-like behaviours and mediate fear-induced antinociception elicited by neuronal activation in the central nucleus of the inferior colliculus. | LitMetric

5-Hydroxytryptamine 2A receptors of the dorsal raphe nucleus modulate panic-like behaviours and mediate fear-induced antinociception elicited by neuronal activation in the central nucleus of the inferior colliculus.

Behav Brain Res

Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Behavioural Neurosciences Institute (INeC), Avenida do Café, 2450, Ribeirão Preto, 14220-030, São Paulo, Brazil. Electronic address:

Published: January 2019

AI Article Synopsis

  • Chemical stimulation of the inferior colliculus (IC) in laboratory animals can trigger panic attack-like behaviors and may also influence pain responses through connections to other brain areas, like the dorsal raphe nucleus (DRN).
  • This study specifically explored the role of 5-HT (serotonin) receptors in the DRN by using a selective antagonist, R-96544, to see how it impacts defensive behaviors and pain relief in Wistar rats after NMDA stimulation of the IC.
  • The results showed that a certain dose of NMDA (12 nmol) was most effective in inducing panic-like behaviors and increased pain tolerance, and these effects were reduced when the DRN was treated with R-96544, highlighting the

Article Abstract

It has been established that chemical stimulation of the inferior colliculus (IC) of laboratory animals evokes fear-related defensive responses, which are considered panic attack-like behaviours. In addition, there is evidence that defensive reactions provoked by chemical stimulation of midbrain tectum neurons may induce an antinociceptive response. Morphologically, the IC receives projections from other mesencephalic structures, such as the dorsal raphe nucleus (DRN), a region rich in serotonergic neurons that play a critical role in the control of defensive behaviours. Moreover, this monoaminergic brainstem reticular nucleus is suggested to comprise the endogenous pain modulatory system. The aim of the present study was to investigate the role of DRN 5-hydroxytryptamine 2A (5-HT) receptors in Wistar rats by local microinjection of R-96544 (a selective antagonist of the 5-HT receptor) at doses of 5, 10 or 15 nM on defensive reactions and fear-induced antinociception evoked by chemical stimulation of the central nucleus of the IC with NMDA (6, 9 or 12 nmol). Behavioural responses were analysed for 10 min, and then the nociceptive threshold was measured at 10 min intervals for 70 min. The dose of 12 nmol of NMDA was the most effective in causing panic attack-like defensive behaviours and much higher hypoalgesia. In addition, both effects were attenuated by pretreatment of the DRN with R-96544. These findings suggest the critical participation of DRN 5-HT receptors in the modulation of panic attack-like defensive behaviour and unconditioned fear-induced antinociception organised by neurons in the central nucleus of the IC.

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http://dx.doi.org/10.1016/j.bbr.2017.07.016DOI Listing

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