Co-treatment with low doses of buspirone prevents rewarding effects of methylphenidate and upregulates expression of 5-HT1A receptor mRNA in the nucleus accumbens

Abstract

Accumulating studies consistently show that methylphenidate (MPD), the first line drug for treating Attention-Deficit Hyperactivity Disorder (ADHD), is abused by patients to whom the drug is prescribed. Like other psychostimulants, only low doses of MPD improve cognitive performance while higher doses impair it. Preventing the use of high doses of MPD is important for retaining its therapeutic efficacy. Previously, it has been shown that performance in Morris water maze test is improved in rats treated, orally, with MPD in doses of 2.5 mg/kg; but higher doses (5 mg/kg) impair it. The present study is designed to monitor rewarding effects of 2.5 mg/kg MPD in conditioned place preference (CPP) paradigm and its potential inhibition in buspirone co-treated animals. Our results show that rewarding effects of MPD in CPP paradigm are prevented in rats co-treated with buspirone in doses of 0.1 and 0.3 mg/kg. Animals treated with MPD exhibit a downregulation of 5-HT1A receptor mRNA in the nucleus accumbens which is also prevented in rats co-treated with 0.1 and 0.3 mg/kg but not 1.0 and 2.0 mg/kg buspirone. Administration of buspirone in these doses is not rewarding in CPP test and upregulates 5-HT1A receptor mRNA in the nucleus accumbens. The findings suggest that co-use of low doses of buspirone can prevent rewarding effects of MPD to help retain its therapeutic efficacy