Neuroanatomical specificity of conditioned responses to cocaine versus food in mice

Abstract Neural circuits implicated in drug conditioning, craving and relapse overlap extensively with those involved in natural reward and reinforcement. To determine whether specificity could be detected in conditioned brain responses to drugs versus food, male outbred HSD:ICR mice were conditioned to a common environment using either 20 mg/kg cocaine (ip) or a familiar food (under food restriction). The mice were then re-exposed to the same environment without the reinforcer and patterns of brain activation were compared using immunohistochemical detection of Fos. Conditioned place preference tests were conducted first to establish relative potency of each reward and facilitate analysis of correlations between Fos and motivation. Place preference was stronger for cocaine than food. Food- but not cocaine-paired cues increased Fos in the paraventricular hypothalamic nucleus whereas the opposite occurred for prefrontal, cingulate and piriform cortices. Individual differences in cocaine place preference were negatively correlated with Fos in the prefrontal cortex. One difference between drugs and natural reinforcers may be lack of feedback from the periphery for drugs which may circumvent control from the hypothalamus in the development of reinforcement circuits.