mGluR5 positive allosteric modulation enhances extinction learning following cocaine self-administration.

作者：Richard M. Cleva, Megan P. Hicks, Justin T. Gass, Kelly C. Wischerath, Elizabeth T. Plasters, John J. Widholm, M. Foster Olive · 发表于：Behavioral Neuroscience · 年份：2011 · DOI：10.1037/a0022339 · 被引用次数：72 · 研究领域：Neuroscience and Neuropharmacology Research、Memory and Neural Mechanisms、Neurotransmitter Receptor Influence on Behavior

Extinction of classically and instrumentally conditioned behaviors, such as conditioned fear and drug-seeking behavior, is a process of active learning, and recent studies indicate that potentiation of glutamatergic transmission facilitates extinction learning. In this study, the authors investigated the effects of the Type-5 metabotropic glutamate receptors (mGluR5) positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction of cocaine-seeking behavior in rats with a history of intravenous cocaine self-administration. To assess its effects on acquisition and consolidation of extinction learning, CDPPB (60 mg/kg) or vehicle was administered either 20 min prior to, or immediately following, each of 10 extinction sessions, respectively. When administered prior to each extinction session, CDPPB produced a significant reduction in the number of active lever presses on all 10 days of extinction training as compared to vehicle-treated animals. When administered following each extinction session, a significant reduction in the number of active lever presses was observed on the 2nd through 10th day of extinction. Both treatment regimens also reduced the number of extinction-training sessions required to meet extinction criteria. Pre- or postextinction-training administration of CDPPB did not alter responding on the inactive lever and had no effects on open field locomotor activity. These data indicate that positive allosteric modulation o...