Conditioned orienting predicts preference for, and affective response to, amphetamine after multiple exposures in male rats.

Conditioned orienting (OR) is a form of cue-directed behavior that is thought to reflect a behavioral phenotype of increased incentive-motivational processing of conditioned stimuli. Previous research has shown that OR also represents a cognitive phenotype that includes impaired attentional function and response inhibition, increased novelty seeking and, in females, resistance to extinction of conditioned place preference (CPP) for the stimulant drug amphetamine (AMP). The following experiments aim to increase our understanding of the OR cognitive phenotype in drug reward processing in male rats. In the first experiment, preference for AMP in males with or without an OR phenotype is assessed using CPP. In the second experiment, our understanding of OR as a predictor of AMP reward response is expanded by measuring potential behavioral mechanisms including affective and motor response to multiple AMP administrations. The results of the two experiments suggest that while the OR phenotype is not a predictor of resistance to extinction of AMP preference in males, OR as a discrete response variable predicts AMP preference after repeated exposures (i.e., AMP challenge). Moreover, we observed that rats with an OR phenotype had a higher positive affective response, measured via ultrasonic vocalizations (USVs) in the 50 kHz range, after multiple AMP administrations. OR scores predicted USVs but did not alter the gross motor response to AMP. Taken together, these results suggest that orienting behavior is a predictor of AMP preference in males, particularly after multiple exposures, and that one behavioral mechanism that could explain this is that male Orienters have a strong positive affective response to AMP.