Conditioned place preference studies with atomoxetine in an animal model of ADHD: Effects of previous atomoxetine treatment

To investigate the putative rewarding effects of atomoxetine, a non-stimulant medication for Attention-deficit/hyperactivity disorder (ADHD), we conducted conditioned place preference (CPP) tests in an animal model of ADHD, the spontaneously hypertensive rat (SHR). The effects of drug pre-exposure were also evaluated, thus, parallel experiments were done in rats which have undergone 14 days of atomoxetine treatment. The responses of SHR were compared with the rat strain representing the “normal” heterogeneous population, the Wistar rats. Neither rat strain showed significant CPP to atomoxetine. However, previous atomoxetine treatment produced place preference responses in rats, more profoundly in Wistar rats conditioned with the low and moderate atomoxetine doses. In conclusion, acute exposure to atomoxetine does not have any rewarding effect, however, drug pretreatment produces responses characteristic of reward or psychological dependence, more specifically in the “normal” vs. the ADHD animal model. The present findings call for more studies with atomoxetine, especially those that investigate the effects of long-term or chronic drug treatment.

Research highlights
► Acute exposure to atomoxetine has no rewarding effects.
► Repeated atomoxetine treatment produces psychological dependence to the drug.
► The rewarding effect is more profound in the Wistar vs. SHR.