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- Title
A single in vivo cocaine administration impairs 5- HT<sub>1B</sub> receptor-induced long-term depression in the nucleus accumbens.
- Authors
Huang, Chiung‐Chun; Yeh, Che‐Ming; Wu, Mei‐Ying; Hsu, Kuei‐Sen
- 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.
- Subjects
COCAINE; NUCLEUS accumbens; PROSENCEPHALON; SEROTONIN; LONG-term synaptic depression; THERAPEUTICS
- Publication
Journal of Neurochemistry, 2013, Vol 125, Issue 6, p809
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.12227