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bioRxiv · 10.1101/2025.09.26.678801

Dopamine receptor sensitivity and Pavlovian conditioned approach

Amissah, N. K.·Tripi, J. A.·King, C. P.·Meyer, P. J.
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Abstract

Understanding the determinants of individual differences in cue-reactivity and drug sensitivity is critical to identifying neurobiological mechanisms underlying vulnerability to addiction. In this study, we examined the relationship between dopamine D1 and D2 receptor sensitivity and the attribution of incentive salience to reward cues and sensitivity to cocaine. Male Sprague Dawley rats were classified as having high or low sensitivity to the D2 receptor agonist quinpirole, and a subset was tested with the D1 receptor agonist SKF 82958. Cue-reactivity was assessed using a Pavlovian conditioned approach (PavCA) task, which distinguishes between sign-tracking (approach to a cue that predicts reward) and goal-tracking (approach to the site of reward delivery). Cocaine sensitivity was measured by locomotor activity and 50-kHz ultrasonic vocalizations (USVs), a putative measure of appetitive states. High D2 responders exhibited more sign-tracking and greater cocaine-induced USVs than low responders despite no difference in cocaine-induced locomotion. Sign-trackers also showed greater locomotor sensitivity to D1 receptor stimulation than goal-trackers and produced more cocaine-induced USVs. Rats with high sensitivity to both D1 and D2 receptor stimulation showed the strongest sign-tracking behavior and affective response to cocaine. These findings suggest that dopamine receptor sensitivity is associated with the propensity to attribute incentive salience to reward cues and potentially the appetitive effects of cocaine. This dopaminergic phenotype may reflect a mechanism contributing to both individual differences in cue-reactivity and drug responsiveness.

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Amissah, N. K., Tripi, J. A., King, C. P., Meyer, P. J.. 2025-09-28. Dopamine receptor sensitivity and Pavlovian conditioned approach. https://doi.org/10.1101/2025.09.26.678801

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