Mice lacking serotonin 2C receptors have increased affective responses to aversive stimuli

Stephen J Bonasera, A. Katrin Schenk, Evan J. Luxenberg, Xidao Wang, Allan Basbaum, Laurence H. Tecott

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Although central serotonergic systems are known to influence responses to noxious stimuli, mechanisms underlying serotonergic modulation of pain responses are unclear. We proposed that serotonin 2C receptors (5-HT2CRs), which are expressed within brain regions implicated in sensory and affective responses to pain, contribute to the serotonergic modulation of pain responses. In mice constitutively lacking 5-HT2CRs (2CKO mice) we found normal baseline sensory responses to noxious thermal, mechanical and chemical stimuli. In contrast, 2CKO mice exhibited a selective enhancement of affect-related ultrasonic afterdischarge vocalizations in response to footshock. Enhanced affect-related responses to noxious stimuli were also exhibited by 2CKO mice in a fear-sensitized startle assay. The extent to which a brief series of unconditioned footshocks produced enhancement of acoustic startle responses was markedly increased in 2CKO mice. As mesolimbic dopamine pathways influence affective responses to noxious stimuli, and these pathways are disinhibited in 2CKO mice, we examined the sensitivity of footshock-induced enhancement of startle to dopamine receptor blockade. Systemic administration of the dopamine D2/D3 receptor antagonist raclopride selectively reduced footshock-induced enhancement of startle without influencing baseline acoustic startle responses. We propose that 5-HT2CRs regulate affective behavioral responses to unconditioned aversive stimuli through mechanisms involving the disinhibition of ascending dopaminergic pathways.

Original languageEnglish (US)
Article numbere0142906
JournalPloS one
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Receptor, Serotonin, 5-HT2C
serotonin
Dopamine
Acoustics
Modulation
Raclopride
receptors
mice
Dopamine Receptors
Startle Reflex
pain
Assays
Brain
Ultrasonics
dopamine
Pain
acoustics
Dopamine D3 Receptors
fearfulness
vocalization

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Bonasera, S. J., Schenk, A. K., Luxenberg, E. J., Wang, X., Basbaum, A., & Tecott, L. H. (2015). Mice lacking serotonin 2C receptors have increased affective responses to aversive stimuli. PloS one, 10(12), [e0142906]. https://doi.org/10.1371/journal.pone.0142906

Mice lacking serotonin 2C receptors have increased affective responses to aversive stimuli. / Bonasera, Stephen J; Schenk, A. Katrin; Luxenberg, Evan J.; Wang, Xidao; Basbaum, Allan; Tecott, Laurence H.

In: PloS one, Vol. 10, No. 12, e0142906, 01.12.2015.

Research output: Contribution to journalArticle

Bonasera, Stephen J ; Schenk, A. Katrin ; Luxenberg, Evan J. ; Wang, Xidao ; Basbaum, Allan ; Tecott, Laurence H. / Mice lacking serotonin 2C receptors have increased affective responses to aversive stimuli. In: PloS one. 2015 ; Vol. 10, No. 12.
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