5-HT1A receptors in the reinforcing effects of methylphenidate and its
modulation with buspirone
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 can impair it. Preventing the use of high doses of
MPD is important for preventing its overuse and for retaining its
therapeutic efficacy. Previously, we have shown that performance in
Morris water test was improved in rats treated, orally, with MPD in
doses of 2.5 mg/kg; but higher doses (5 mg/kg) impaired it. The present
study concerns rewarding/reinforcing effects of 2.5 mg/kg MPD in
conditioned place preference (CPP) paradigm and its modulation with
buspirone. Our results show that rewarding effects of MPD in CPP test
are prevented in rats co-treated with buspirone in doses of 0.1 and 0.3
mg/kg. Animals treated with MPD exhibit a down regulation of 5-HT1A
receptor in the nucleus accumbens which is reversed in rats co-treated
with 0.1 an 0.3 mg/kg buspirone. Administration of buspirone in these
doses is not rewarding in CPP test and produces an upregulation of
5-HT1A receptor in the nucleus accumbens. The findings suggesting an
important role of 5-HT1A receptor in the rewarding effects of MPD, open
a gateway for improving therapeutic use of MPD.