Nicotinic receptors differentially modulate the induction and expression of behavioral sensitization to methylphenidate in rats

Nicotinic acetylcholine receptors (nAChRs) regulate sensitization to stimulant drugs such as d-amphetamine and cocaine. The current study determined if nAChRs modulate the induction and/or expression of behavioral sensitization to high methylphenidate doses. In experiment 1, rats received saline or mecamylamine (3 mg/kg, sc), followed by saline or methylphenidate (5.6 or 10 mg/kg, sc) during 10 daily sessions; the effect of methylphenidate (1-17 mg/kg, sc) alone was determined 14 days later. In experiment 2, rats received saline or dihydro-beta-erythroidine (DH beta E; 3 mg/kg, sc), followed by saline or 5.6 mg/kg of methylphenidate. In experiment 3, rats received saline or methylphenidate (5.6 or 10 mg/kg, sc) alone for 10 days; the effect of acute mecamylamine (3 mg/kg, sc) on the response to methylphenidate (1-17 mg/kg, sc) was determined 14 days later. Locomotor activity, sniffing, rearing, grooming, and stereotypy ratings were dependent measures. Methylphenidate produced dose-dependent increases in locomotor activity, sniffing, and stereotypy on day 1 and these effects were enhanced on day 10, indicative of sensitization. Mecamylamine attenuated methylphenidate-induced stereotypy only on day 1, but reduced locomotor activity, sniffing, rearing, and stereotypy on day 10 and during the methylphenidate challenge phase; similar results were obtained with DH beta E. However, acute mecamylamine did not alter the effects of the methylphenidate challenge following the induction of sensitization to methylphenidate alone. Although nAChRs do not appear to regulate the expression of methylphenidate-induced behavioral sensitization, inhibition of high-affinity beta 2 subunit nAChRs attenuates the induction of behavioral sensitization to high doses of methylphenidate.