Abstract
The stimulant, methylphenidate (MPH), is commonly used to treat attention deficit hyperactivity disorder (ADHD) and has been increasingly prescribed for school age children and adolescents. Concerns regarding its long-term effects on later substance use disorders (SUDs) have been raised. Previous animal studies have produced contradictory results regarding whether early exposure to MPH increases or protects against SUD in adulthood. The goal of our study was to determine if clinically relevant doses of MPH during adolescence alter cocaine responsiveness in adulthood in a rat model of ADHD, the spontaneous hypertensive rat (SHR). We pretreated SHRs with saline or MPH (2.5 mg/kg once or twice day) via oral gavage during their dark cycle from postnatal day 35 (p35) to p44. Adult rats (p80) were assessed in an eight-session cocaine-conditioned place preference test (CPP). Four doses of cocaine were administered via intraperitoneal injection (i.p.) during the conditioning sessions: 1, 5, 10 and 20 mg/kg. Once per day MPH treatment had a small sensitizing effect on baseline general locomotor activity in a novel environment at p80 as well as a limited suppressive effect on reward-specific locomotor activity as measured by the decreased preference to enter the cocaine-paired chamber. This treatment did not have any effect on the amount of time that rats chose to spend in the cocaine-paired chamber. Twice per day MPH treatment had no effect on locomotion or drug-preference. Our results suggest that MPH treatment of ADHD rats during adolescence does not alter preference for cocaine in adulthood.
Highlights
The stimulant methylphenidate (MPH) treats attention deficit hyperactivity disorder (ADHD) [1] and is often prescribed for prolonged periods given that the disorder persists into adulthood in two-thirds of cases [2]
Animal models are widely used in studies of childhood and adolescent MPH treatment effects on adult substance abuse behaviors
Addressing this issue in a manner that is relevant to the clinical treatment of ADHD requires selecting the proper MPH dose and the route and timing of drug administration
Summary
The stimulant methylphenidate (MPH) treats attention deficit hyperactivity disorder (ADHD) [1] and is often prescribed for prolonged periods given that the disorder persists into adulthood in two-thirds of cases [2]. MPH increases extracellular dopamine by blocking the dopamine transporter (DAT). This mechanism underlies both its therapeutic and reinforcing effects [3]. MPH is abused by adolescents and adults [4,5,6] and the diversion and misuse of ADHD medications is a clinical concern [7,8]. A slow uptake of medication in the brain via oral treatment has a lower potential for abuse or diversion [10], it is still not clear whether long-term exposure to therapeutic dose of MPH during youth alters the risk for substance abuse in adulthood
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