Effects of amphetamine, methylphenidate, atomoxetine, and morphine in rats responding under an adjusting stop signal reaction time task

Abstract

Stop signal reaction time procedures are used to investigate behavioral and neurobiological processes that contribute to behavioral inhibition and to evaluate potential therapeutics for disorders characterized by disinhibition and impulsivity. The current study examined effects of amphetamine, methylphenidate, atomoxetine, and morphine in rats responding under an adjusting stop signal reaction time task that measures behavioral inhibition, as well as motor impulsivity. Rats (n = 8) completed a two-response sequence to earn food. During most trials, responses following presentation of a visual stimulus (go signal) delivered food. Occasionally, a tone (stop signal) was presented signifying that food would be presented only if the second response was withheld. Responding after the stop signal measured inhibition and responding prior to the start of the trial (premature) measured motor impulsivity. Delay to presentation of the stop signal was adjusted for individual subjects based on performance. Amphetamine and methylphenidate increased responding after presentation of the stop signal and markedly increased premature responding. Atomoxetine modestly improved accuracy on stop trials and decreased premature responding. Morphine did not alter stop trial accuracy or premature responding up to doses that decreased the number of trials initiated. These data demonstrate the sensitivity of an adjusting stop signal reaction time task to a range of drug effects and shows that some drugs that enhance dopaminergic transmission, such as amphetamine, can differentially alter various types of impulsive behavior.