One-trial behavioral sensitization in preweanling rats: differential effects of cocaine, methamphetamine, methylphenidate, and D-amphetamine.

RATIONALE: Preweanling rats exhibit robust one-trial cocaine-induced behavioral sensitization; however, it is uncertain whether other psychostimulants can also induce sensitization in young rats using the one-trial procedure. OBJECTIVE: The purpose of this study was to determine whether methamphetamine, methylphenidate, and D: -amphetamine are capable of inducing one-trial locomotor sensitization in preweanling rats. METHODS: In a series of four experiments, rats were pretreated with cocaine (30 mg/kg), methamphetamine (2-12 mg/kg), methylphenidate (5-20 mg/kg), or amphetamine (5 mg/kg) before being placed in a novel activity chamber or the home cage on PD 19. Rats were then challenged with the same psychostimulant (20 mg/kg cocaine, 1-8 mg/kg methamphetamine, 2.5-7.5 mg/kg methylphenidate, or 1-2 mg/kg amphetamine) on PD 21, with distance traveled being measured for 180 min. In a separate experiment, rats were pretreated with methamphetamine on PD 16-19 and challenged with methamphetamine on PD 21. RESULTS: Only cocaine, but not various dose combinations of other psychostimulants, was able to produce one-trial behavioral sensitization in preweanling rats. Context-dependent locomotor sensitization was also evident if rats were pretreated with methamphetamine on PD 16-19 and tested on PD 21. CONCLUSIONS: It is uncertain why only cocaine was able to induce one-trial locomotor sensitization in preweanling rats, but it is possible that: (a) the neural circuitry mediating sensitization differs according to psychostimulant, (b) cocaine is more readily associated with environmental contexts than other psychostimulants, or (c) affinity and pharmacokinetic factors may underlie cocaine's ability to induce one-trial behavioral sensitization in preweanling rats.

Early methylphenidate exposure enhances cocaine self-administration but not cocaine-induced conditioned place preference in young adult rats.

RATIONALE: Previous studies in rodents show that early exposure to methylphenidate alters later responsiveness to drugs of abuse. An interesting feature of these studies is that early methylphenidate treatment decreases the rewarding value of cocaine when measured by conditioned place preference (CPP), but the same treatment increases cocaine self-administration. OBJECTIVE: The goal of the present study was to examine the effects of early methylphenidate exposure on cocaine-induced responding using both reward paradigms. METHODS: Rats were treated with methylphenidate (0, 2, or 5 mg/kg) from postnatal days (PDs) 11 to 20, and then cocaine-induced CPP or cocaine self-administration was measured in separate groups of rats in adulthood. The CPP procedure included 8 days of acquisition training, 8 days of extinction training, and a reinstatement test. Rats were conditioned with 0, 10, or 20 mg/kg cocaine. Reinstatement was assessed after a priming dose of cocaine (10 mg/kg). For the self-administration experiment, a jugular catheter was implanted and rats were trained to press a lever reinforced with cocaine (0.25 or 0.75 mg/kg/infusion) on a fixed ratio (FR) one schedule. Rats were gradually moved from an FR1 to an FR10 schedule and, after criterion was reached, rats were placed on a progressive ratio schedule for 5 days. RESULTS: Cocaine produced robust rewarding effects as determined by both the CPP and self-administration experiments; however, early methylphenidate exposure only enhanced the reinforcing effects of cocaine on the self-administration paradigm. Interestingly, this methylphenidate enhancement was only seen in male rats. CONCLUSIONS: These data suggest that in males, methylphenidate enhances the reinforcing value of cocaine, but not cocaine-associated cues.