Oral methylphenidate establishes a conditioned place preference in rats

Abstract

Emerging data suggest that illicit methylphenidate abuse is a growing problem. Although abuse of the drug typically occurs by the intranasal route, oral (per os; p.o.) methylphenidate also has abuse potential. The present study compared the effects of p.o. and intraperitoneal (i.p.) methylphenidate in rats using the conditioned place preference (CPP) procedure. Young adult male Sprague-Dawley rats were trained to consume oyster crackers injected initially with saline. Next, rats were randomly assigned to receive p.o. or i.p. methylphenidate (3 or 10 mg/kg) or saline immediately or 30 min prior to 30-min conditioning trials. Methylphenidate or saline were each paired 4 times with an end compartment; preference for the methylphenidate-paired compartment was then assessed on a drug-free session. When given immediately prior to conditioning, significant CPP was obtained with both 3 and 10 mg/kg of i.p. methylphenidate, but only with 10 mg/kg of p.o. methylphenidate. When given 30 min prior to conditioning, there was no evidence of CPP for any dose of i.p. or p.o. methylphenidate. These findings are the first demonstration that p.o. methylphenidate has rewarding effects, although i.p. methylphenidate is obtained at a 3 mg/kg dose which did not establish CPP with p.o. administration. The lack of CPP following 30 min pretreatment also suggests that conditioning may require the CS to be associated with a US of ascending, rather than descending, brain levels of methylphenidate. These results are consistent with clinical evidence of the reduced abuse liability of p.o. methylphenidate relative to methylphenidate taken by other (e.g., intranasal) routes.

Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice

“…An important finding from the CPP studies is that the 1.25 mg/kg dose of MPH supported significant place preference, consistent with other recent reports investigating smaller doses of MPH (3 mg/kg or less) in the context of reward (dela Peña et al 2012; dela Peńa et al 2011; Trezza et al 2009; Wooters et al 2011). Interestingly, another recent report found that 0.75 mg/kg MPH did not support place preference in contrast to a 10-fold higher dose (Zhu et al 2011b), suggesting a lower limit to the reinforcing effects of MPH.…”

Single and Repeated Administration of Methylphenidate Modulates Synaptic Plasticity in Opposite Directions via Insertion of AMPA Receptors in Rat Hippocampal Neurons

“…Consistent with the decrease of the number of GluA1 subunits in the membrane, we also found a significant reduction of the AMPA-mediated EPSC and short-term plasticity in slices from rats treated repeatedly with MPH. A decrease in the AMPA-mediated EPSC has also been observed in NAc slices prepared from young mice treated for 5 days with cocaine (Wooters et al, 2011). This reduction is consistent with previous evidence showing that repeated amphetamine administration decreases the levels of GluA1 and GluA2 mRNA in NAc at day 14 of withdrawal time (Lu et al, 1997).…”

The Role of Dopamine D₁ and D₂ Receptors in Adolescent Methylphenidate Conditioned Place Preference: Sex Differences and Brain-Derived Neurotrophic Factor

“…dose; CPP to MPH was blocked by the general dopamine antagonist cis-flupenthixol. Wooters et al [14] showed that intraperitoneal administration of 3 or 10 mg/kg MPH produced CPP, but only a high dose of orally administered MPH (10 mg/kg) produced CPP. Interestingly, there are only two studies which have analyzed MPH CPP in adolescent animals.…”