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A single in vivo cocaine administration impairs 5‐ HT 1B receptor‐induced long‐term depression in the nucleus accumbens
Author(s) -
Huang ChiungChun,
Yeh CheMing,
Wu MeiYing,
Hsu KueiSen
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12227
Subject(s) - nucleus accumbens , synapsin i , serotonergic , dopamine , chemistry , glutamatergic , long term depression , forebrain , medium spiny neuron , nmda receptor , pharmacology , serotonin , glutamate receptor , neuroscience , receptor , endocrinology , biology , striatum , ampa receptor , central nervous system , biochemistry , vesicle , membrane , synaptic vesicle
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‐HT 1B 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 D 1 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‐HT 1B 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‐HT 1B receptors and thereby impairs the induction of LTD by 5‐HT.