Performance on a strategy set shifting task during adolescence in a genetic model of attention deficit/hyperactivity disorder: Methylphenidate vs. atomoxetine treatments

Abstract

Research examining medication effects on set shifting in teens with attention deficit/hyperactivity disorder (ADHD) is lacking. An animal model of ADHD may be useful for exploring this gap. The spontaneously hypertensive rat (SHR) is a commonly used animal model of ADHD. SHR and two comparator strains, Wistar-Kyoto (WKY) and Wistar (WIS), were evaluated during adolescence in a strategy set shifting task under conditions of a 0s or 15s delay to reinforcer delivery. The task had three phases: initial discrimination, set shift and reversal learning. Under 0s delays, SHR performed as well as or better than WKY and WIS. Treatment with 0.3mg/kg/day atomoxetine had little effect, other than to modestly increase trials to criterion during set shifting in all strains. Under 15s delays, SHR had longer lever press reaction times, longer latencies to criterion and more trial omissions than WKY during set shifting and reversal learning. These deficits were not reduced systematically by 1.5mg/kg/day methylphenidate or 0.3mg/kg/day atomoxetine. Regarding learning in SHR, methylphenidate improved initial discrimination, whereas atomoxetine improved set shifting but disrupted initial discrimination. During reversal learning, both drugs were ineffective in SHR, and atomoxetine made reaction time and trial omissions greater in WKY. Overall, WIS performance differed from SHR or WKY, depending on phase. Collectively, a genetic model of ADHD in adolescent rats revealed that neither methylphenidate nor atomoxetine mitigated all deficits in SHR during the set shifting task. Thus, methylphenidate or atomoxetine monotherapy may not mitigate all set shift task-related deficits in teens with ADHD.