The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats

Rationale: The metabotropic glutamate (mGlu5) receptor subtype 5 antagonist MPEP attenuates self-administration of numerous drugs of abuse. Objectives: The purpose of the present study was to explore whether MPEP-induced decreases in nicotine and cocaine self-administration reflect attenuation of the reinforcing and incentive motivational effects of nicotine and cocaine. The effects of MPEP on breaking points maintained by nicotine, cocaine or food were assessed using a progressive ratio schedule of reinforcement. Breaking points obtained under such schedules are postulated to reflect both the reinforcing and incentive motivational properties of reinforcers. Methods: Rats were allowed to respond for nicotine (0.05 mg/kg per infusion, free base), cocaine (0.18 mg/kg per infusion, salt), or food (45 mg pellets) under a progressive ratio schedule of reinforcement. After establishing stable and equivalent levels of responding for all three reinforcers, rats underwent one test session where no rewards were presented to assess the effects of 1-day extinction, similar to 1-day pharmacological-induced extinction, on performance in this schedule. Subsequently, rats were again allowed to respond for nicotine, cocaine or food until reestablishment of stable levels of responding. Then, MPEP (1-9 mg/kg) was administered intraperitoneally according to a within-subjects Latin square design, 30 min prior to the testing sessions. Results: Responding in the absence of a primary reinforcer was significantly decreased compared to responding under baseline conditions. Further, MPEP decreased break points maintained by nicotine, cocaine and food. Conclusions: The mGlu5 receptor is implicated in mediating the reinforcing and incentive motivational properties of nicotine, cocaine and food.