A single in vivo cocaine administration impairs 5-HT1B receptor-induced long-term depression in the nucleus accumbens

Chiung Chun Huang, Che Ming Yeh, Mei Ying Wu, Kuei Sen Hsu

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

The nucleus accumbens (NAc) is a crucial forebrain nucleus implicated in reward-based decision-making. While NAc neurons are richly innervated by serotonergic fibers, information on the functional role of serotonin 5-hydroxytryptamine (5-HT) in the NAc is still sparse. Here, we demonstrate that brief application of 5-HT or 5-HT1B receptor agonist CP 93129 induced a long-term depression (LTD) of glutamatergic transmission in NAc neurons. This LTD was presynaptically mediated and inducible by endogenous 5-HT. Remarkably, a single cocaine exposure impaired the induction of LTD by 5-HT or CP 93129. The inhibition was blocked when a selective dopamine D1 receptor antagonist SCH23390 was coadministered with cocaine. Cocaine treatment resulted in increased phosphorylation of presynaptic proteins, rabphilin 3A and synapsin 1, and significantly attenuated CP 93129-induced decrease in rabphilin 3A and synapsin 1 phosphorylation. Application of cAMP-dependent protein kinase inhibitor KT5720 caused a prominent synaptic depression in NAc neurons of mice with a history of cocaine exposure. Our results reveal a novel 5-HT1B receptor-mediated LTD in the NAc and suggest that cocaine exposure may result in elevated phosphorylation of presynaptic proteins involved in regulating glutamate release, which counteracts the presynaptic depressant effects of 5-HT1B receptors and thereby impairs the induction of LTD by 5-HT. We investigate whether dysregulation of serotonergic modulation of glutamatergic transmission in the NAc would have a significant role in the development of cocaine addiction. We find that a single in vivo exposure to cocaine impairs the induction of 5-HT-LTD in the NAc. It provides major advances in our understanding of the functional role of the 5-HT system in the NAc.

Original languageEnglish
Pages (from-to)809-821
Number of pages13
JournalJournal of Neurochemistry
Volume125
Issue number6
DOIs
Publication statusPublished - 2013 Jun

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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