Environmental enrichment during development decreases intravenous self-administration of methylphenidate at low unit doses in rats

Abstract

Despite the efficacy and widespread use of methylphenidate (MPH) as a treatment for Attention Deficit Hyperactivity Disorder (ADHD), clinical and preclinical findings indicate it has abuse potential. Environmental enrichment reduces susceptibility to cocaine and amphetamine self-administration, and decreases impulsive behavior, but its effects on MPH self-administration are unknown. The present experiments sought to determine the influence of environmental enrichment on MPH self-administration. Male rats were raised in an enriched condition (EC) or isolated condition (IC). They were trained to self-administer MPH (0.3 mg/kg/infusion) and then exposed to varying doses of MPH on either a fixed ratio (FR; Experiment 1) or progressive ratio (PR; Experiment 2) schedule of reinforcement. EC rats earned significantly fewer infusions of MPH at low doses (0.03 and 0.056 mg/kg/infusion) than IC rats under both schedules; however, no differences were observed at high unit doses (0.1–1.0 mg/kg/infusion). During saline substitution at the end of MPH self-administration, EC rats also responded less for saline than IC rats, indicative of more rapid extinction. As with other stimulant drugs with different mechanisms of action, environmental enrichment during development protects against self-administration of MPH at low unit doses, but not at high unit doses.

Environmental enrichment reduces methamphetamine cue-induced reinstatement but does not alter methamphetamine reward or VMAT2 function

“…Cue-elicited reinstatement of METH seeking also was decreased in EC rats following a period of response extinction. Even though these results parallel those obtained with amphetamine, cocaine, and methylphenidate [4, 6, 7], they were obtained after differential rearing, rather than during differential rearing as in previous studies. Moreover, a limitation of this study was that the training dose of METH (0.03 mg/kg) failed to produce reliable acquisition of self-administration in EC rats, i.e., nose-poking for METH did not differ between acquisition sessions 1 and 8.…”

“…In contrast to CPP, however, the direct reinforcing effect of stimulants is decreased by enrichment. EC rats self-administer less cocaine [4], methylphenidate [6], and amphetamine [7] at low unit doses (0.008–0.1 mg/kg/infusion cocaine; 0.056 mg/kg/infusion methylphenidate; 0.03 mg/kg/infusion amphetamine), but not at higher unit doses, relative to IC rats. EC rats also fail to reinstate extinguished responding following a dose of amphetamine (0.25 mg/kg) that reinstates responding in IC rats [8]; a higher dose of amphetamine (1 mg/kg) reinstates responding in both groups.…”

“…The differential rate of acquisition between EC and IC rats complicates interpretation of the subsequent assessment of extinction and reinstatement testing. One way to limit this complication is to use a high training dose in order to initially engender comparable responding in EC and IC groups [4, 6]. This procedure also allows for a more direct comparison to existing literature to determine if enrichment has a differential effect on METH reward compared to other stimulant drugs.…”

Effects of chronic methylphenidate in adolescence on later methylphenidate self-administration in rhesus monkeys

“…When cocaine reinforcement was studied, prior MPH treatment did not increase vulnerability (Gill et al, 2012). In addition to its therapeutic effects, MPH has abuse liability, especially in young adults (Boyd et al, 2006), and can function as a reinforcer under several conditions in animal models (e.g., Johanson and Schuster, 1975; Bergman et al, 1989; Lile et al, 2003; Alvers et al, 2012; see Kollins et al, 2001 for review). However, the effect of adolescent MPH treatment on subsequent MPH self-administration has not been examined, and was the goal of the present study.…”

Effects of environmental enrichment on d-amphetamine self-administration following nicotine exposure.

“…Studies using an enrichment model similar to those used by Bardo and colleagues, have found that rats raised in enriched environments (EC) show a decrease in the sensitivity to the behavioral effects of stimulants compared to rats raised in isolated conditions (IC; (Bardo et al, 1995; Stairs & Bardo, 2009)). In rats, environmental enrichment decreased self-administration of low unit doses of d-amphetamine, methylphenidate and cocaine (Alvers, Marusich, Gipson, Beckmann, & Bardo, 2012; Bardo, Klebaur, Valone, & Deaton, 2001; Gipson, Beckmann, El-Maraghi, Marusich, & Bardo, 2011; Green, Gehrke, & Bardo, 2002). …”