title: A single in vivo cocaine administration impairs 5-HT(1B) receptor-induced long-term depression in the nucleus accumbens.
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.
authors: Department of Pharmacology, Tainan, Taiwan.
authors: Chiung-Chun
authors: CC
authors: Huang
authors: Che-Ming
authors: CM
authors: Yeh
authors: Mei-Ying
authors: MY
authors: Wu
authors: Kuei-Sen
authors: KS
authors: Hsu
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017661:Receptors, Presynaptic / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D017447:Receptors, Dopamine D1; D017661:Receptors, Presynaptic; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D003042:Cocaine