Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats
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- 作者：Anton Y. Bespalov ; Olga A. Dravolina ; Ilya Sukhanov ; Elena Zakharova ; Elena Blokhina ; Edwin Zvartau ; Wojciech Danysz ; Gino van Heeke ; Athina Markou
- 关键词：Nicotine self-administration ; Cue-induced reinstatement ; Schedule-induction ; Metabotropic glutamate receptor ; mGluR5 ; MPEP ; Rat
- 刊名：Neuropharmacology
- 出版年：2005
- 出版时间：2005
- 年：2005
- 卷：49
- 期：Supplement 1
- 页码：167-178
- 全文大小：289 K
文摘
Previous studies suggested that metabotropic glutamate 5 (mGlu5) receptors play an important role in the reinforcing effects of abused drugs. The present experiments evaluated the effects of the mGlu5 receptor antagonist, MPEP (2-methyl-6-(phenylethynyl)-pyridine hydrochloride; 1–10 mg/kg, salt, i.p.), in rat models of nicotine-seeking behavior that may have relevance to relapse to drug-taking. Male Wistar rats (with restricted access to food) were trained to nose-poke to receive intravenous infusions of nicotine (0.03 mg/kg per infusion, base) under a fixed ratio 5 time out 60 s schedule of reinforcement. After stable nicotine self-administration was acquired, nose-poking behavior was extinguished in the absence of nicotine-associated cues. During the reinstatement test phase, independent groups of animals were exposed to: (a) response-contingent nicotine-associated cues (cue-induced reinstatement); or (b) response-noncontingent presentations of 45-mg food pellets under fixed time 2 min schedule (schedule-induced reinstatement). Additional control experiments were conducted to demonstrate that in nicotine-naïve animals MPEP does not affect cue-induced reinstatement of food-seeking behavior and has no effects on operant behavior maintained by a simple fixed interval 2 min schedule of food reinforcement. Pretreatment with MPEP (10 mg/kg) significantly attenuated the reinstatement of nicotine-seeking in both experiments. Further, MPEP (10 mg/kg) significantly attenuated polydipsia induced by a fixed time 2 min food schedule. In conclusion, the present findings indicate that the blockade of mGlu5 receptors attenuates cue-induced reinstatement of nicotine self-administration behavior (but not food-seeking) and may produce a general inhibition of schedule-induced behaviors, including schedule-induced nicotine-seeking.