Regulation of cocaine-reinstated drug-seeking behavior by κ-opioid receptors in the ventral tegmental area of rats
| Autor: | YueQiang Xue, ZaiFang Huang, Jeffery D. Steketee, Wen Lin Sun |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Drug Dopamine media_common.quotation_subject Pharmacology Amygdala Article Rats Sprague-Dawley Cocaine-Related Disorders Recurrence medicine Animals Prefrontal cortex media_common Dose-Response Relationship Drug Mechanism (biology) Receptors Opioid kappa Addiction Ventral Tegmental Area 3 4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide (trans)-Isomer Rats Ventral tegmental area medicine.anatomical_structure Opioid Conditioning Operant Psychology Neuroscience medicine.drug |
| Zdroj: | Psychopharmacology. 210:179-188 |
| ISSN: | 1432-2072 0033-3158 |
| DOI: | 10.1007/s00213-010-1812-0 |
| Popis: | Relapse is one of the main challenges facing the current treatment of cocaine addiction. Understanding its neurobiological mechanism is a critical step toward developing effective anti-relapse therapies.Emerging evidence indicates that glutamate-mediated activation of dopamine (DA) neurons in the ventral tegmental area (VTA) may be critically involved in cocaine-induced relapse to drug-seeking behavior. Activity of VTA DA neurons is modulated by multiple neurotransmitter systems including opioids, serotonin, dopamine, and acetylcholine. Recent studies demonstrated that activation of kappa-opioid receptors (kappaORs) in the rat VTA directly inhibits the activity of a subpopulation of DA neurons projecting to the prefrontal cortex (PFC) and amygdala. Because we previously showed that blockade of DA receptors in the dorsal PFC inhibits cocaine-induced reinstatement of extinguished cocaine-seeking behavior suggesting a critical role of the VTA-PFC DA circuit in this process, we tested the hypothesis that activation of kappaORs in the VTA will block cocaine-induced reinstatement in rats.Rats were trained to self-administer intravenous cocaine (0.125 mg/infusion) under a modified fixed-ratio five schedule. After extinction of the learned behavior, the effects of activation of VTA kappaORs on cocaine-induced reinstatement were studied.The kappaOR agonist U50 488 (0-5.6 microg/side) microinjected into the VTA dose-dependently decreased cocaine-induced reinstatement. The effects could not be explained by either a disruption of operant behavior or diffusion of the drug to the areas surrounding the VTA. Moreover, the effect was reversed by norbinaltorphimine.The VTA DA neurons expressing functional kappaORs are critically involved in cocaine-induced reinstatement in rats. |
| Databáze: | OpenAIRE |
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