Activation of the dorsal cerebellum and ventral tegmental area in the expression of cocaine-conditioned place preference in mice.

Abstract

Addictive drugs are potent neurophysiological agents capable of inducing long-lasting changes in brain circuits responsible for learning and memory. The high risk of relapse, characteristic of addiction, is triggered by exposure to the environment in which drugs are administered. The neuroplasticity underlying drug-induced memories recruits the prefrontal-limbic-striatal networks. Medial Prefrontal Cortex (mPFC) and Ventral Tegmental Area (VTA), together with other regions, are critical areas in the acquisition of drug-conditioned memories. Current data suggest the involvement of the cerebellum in the circuitry responsible for drug addiction. The aim of this study was twofold. First, to examine whether the administration of cocaine following a fixed or ascending schedules produces differences in the acquisition of conditioned place preference in mice. Second, to investigate the pattern of neural activation in the mPFC, VTA and dorsal cerebellum (lobule VIII and IX) in mice trained in cocaine-CPP using both, fix and ascending schedules. Male CD-1 mice were trained using a place preference procedure with tactile cues either with fix or ascending doses of cocaine. Our results indicate that an ascending schedule of cocaine dose administration facilitated acquisition of CPP increasing the number of subjects that acquire cocaine-CPP. The activation of the dorsal part of the cerebellum, together with the VTA, are associated with the expression of cocaine-induced CPP. Activity in the PL cortex was not related to CPP. Taken together, these findings suggest that the dorsal region of cerebellum, and the VTA could work together, as part of the same network that mediates the expression of cocaine-conditioned behavior.