Strain differences in self-administration of methylphenidate and sucrose pellets in a rat model of attention-deficit hyperactivity disorder

Abstract

Despite its abuse potential, methylphenidate (MPH) is widely prescribed for treatment of attention-deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine MPH self-administration in a rat model of ADHD. Experiment 1 examined the acquisition of MPH self-administration and assessed the MPH dose-effect curve in spontaneously hypertensive rats (SHR), an inbred rat model of ADHD, Wistar Kyotos (WKY), the progenitor strain for SHR, and Sprague-Dawley (SD), an outbred control strain. Experiment 2 replicated Experiment 1, but replaced MPH infusions with sucrose pellets. Initial acquisition of MPH self-administration was greater in SHR and SD than WKY. However, with extended training using an incrementing fixed ratio schedule SHR and WKY did not differ in responding for MPH using the training dose (0.3 mg/kg/infusion) or other unit doses, except that SHR showed greater responding than WKY at 0.1 mg/kg/infusion. SHR also showed greater acquisition and maintenance of sucrose-reinforced responding compared with both WKY and SD. Greater initial acquisition of MPH self-administration in SHR than WKY may not be due to a strain-specific difference in sensitivity to the reinforcing effect of MPH. Behavioural Pharmacology 22:794-804 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins