Differential behavioral responses of the spontaneously hypertensive rat to methylphenidate and methamphetamine: lack of a rewarding effect of repeated methylphenidate treatment

Several questions remain unanswered concerning the effects of long-term methylphenidate treatment in individuals with attention-deficit/hyperactivity disorder (ADHD). It has been speculated that repeated methylphenidate treatment may facilitate abuse of the drug or psychological dependence. In the present study, we conducted conditioned place preference (CPP) tests to investigate whether the repeated treatment of methylphenidate results to greater “liking” of the drug. We compared the effect of methylphenidate with that of methamphetamine, a drug with high abuse and dependence liability; also used as a treatment of ADHD. Prior to CPP tests, adolescent spontaneously hypertensive rats (SHR) (putative rodent model of ADHD) and Wistar rats (strain used to represent the “normal” heterogeneous population) were administered intraperitoneally with methylphenidate (1.25, 5 and 20 mg/kg) or methamphetamine (1.25 and 5 mg/kg) for 14 days in their home cages. CPP tests were commenced and rats were conditioned with the two stimulants at the doses stated. We found that (1) repeated administration of methylphenidate and methamphetamine was rewarding in Wistar rats (2) stimulant-treated SHR showed CPP only to methamphetamine but not to methylphenidate. The observation that Wistar rats, but not SHR showed CPP to methylphenidate indicates vulnerability of “normal” individuals to methylphenidate abuse and dependence following repeated exposure or administration of the drug. The findings in SHR suggest the safety of methylphenidate as an ADHD intervention insofar as its behavioral effects are compared with those of methamphetamine, and to the extent that the SHR appropriately models ADHD in humans.

► The rewarding effect of repetitive methylphenidate and methamphetamine treatment was compared in SHR.
► SHR showed CPP to repeated methylphenidate but not methylphenidate treatment.
► Long-term use of methylphenidate may not produce psychological dependence in individuals with ADHD.