Oral Methylphenidate Treatment of an Adolescent ADHD Rat Model Does Not Alter Cocaine-Conditioned Place Preference during Adulthood: A Negative Report

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 Open Access

Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review

“…A two-bottle paradigm model did not demonstrate any significant effect on cocaine CPP [90]. Other studies using the two-bottle paradigm have shown similar results: MP oral exposure does not exacerbate cocaine CPP [71]. However, IP injection of MP induced CPP when delivered at a 5 mg/kg dose [89].…”

“…The most commonly used dosage of MP through the oral gavage method is 2.5 mg/kg, mainly due to its calming effects shown in "ADHD rats". However, this dose contrarily causes an excitatory response in wild type rats [71]. Doses used in other studies include 0.5-5 mg/kg, with 5 mg/kg on the higher end of the spectrum and commonly used to mirror illicit use of MP [72].…”