Amphetamine influences conditioned response timing and laterality of anterior cingulate cortex activity during rabbit delay eyeblink conditioning

Previous studies have shown that amphetamine can enhance learning in Pavlovian conditioning tasks, but little is known about the changes in neural activity accompanying these performance enhancements. We evaluated the effects of amphetamine (10 μmol/kg) on delay eyeblink conditioning performance and single-neuron activity in the anterior cingulate cortex (area 24) of the rabbit (Oryctolagus cuniculus). Amphetamine produced little to no learning enhancement on our task but strongly influenced the conditioned response (CR), which peaked closer in time to the onset of the unconditioned stimulus (US). The overall ACC population response showed very weak stimulus-evoked modulations during the course of training, with the primary effect being an increase in inhibition. Group discrepancies in stimulus-evoked inhibition correlated with differences in learning performance, and this correlation was stronger when subjects were grouped according to learning performance, independent of drug treatment. ACC neuronal responses of both groups displayed hemispheric asymmetries (laterality), but amphetamine treatment altered this effect, in that activity within each hemisphere of the amphetamine group more closely resembled that of the contralateral hemisphere of controls. Our data suggest that amphetamine modulates CR timing, and influences the flow of sensory information to the two cortical hemispheres. Our observations are also consistent with the ACC’s non-essential role in learning during delay eyeblink conditioning.