Effects of risperidone on development and expression of nicotine-induced locomotor sensitization in rats

It has been shown that atypical antipsychotics significantly reduce smoking and alcohol consumption in schizophrenic patients. However, our knowledge about the effect of risperidone, especially on nicotine abuse is limited. We aimed to test the effects of risperidone in an animal model of nicotine-induced locomotor sensitization, which represents initial neuroadaptations and continued behavioral changes in nicotine-type dependence. To investigate the effect of risperidone on the development of nicotine-induced locomotor sensitization, rats were pretreated with risperidone (0.025 and 0.050 mg kg⁻¹) 30 min before the nicotine (0.5 mg kg⁻¹, base) treatment, and locomotor activity was recorded for 30 min. This procedure was repeated every day for eight sessions. After a 6-day drug-free period, rats were challenged with nicotine (0.5 mg kg⁻¹). To reveal the effect of risperidone on the expression of nicotine-induced locomotor sensitization, rats were injected with nicotine for eight sessions. After a 6-day drug-free period, rats were pretreated with risperidone (0.025 and 0.050 mg kg⁻¹) or vehicle 30 min before the nicotine (0.5 mg kg⁻¹) challenge injection. Repeated administration of nicotine generated robust locomotor sensitization in rats. Risperidone pretreatment (0.050 mg kg⁻¹) blocked the expression but not the development of nicotine-induced locomotor sensitization in rats. Our results suggest that risperidone blocks the continuation of nicotine-type addictive behavior, but it is ineffective on early adaptations in the initiation of nicotine addiction. Thus, this drug may have a limited beneficial effect in treatment of nicotine dependence.