Plasticity in the prelimbic cortex a lesion of the dorsal cerebellar cortex in rats trained to acquire cocaine-induced preference conditioning

Abstract

Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. Drug seeking derives from an over-consolidation of such drug-dependent Pavlovian memories in the striatum-cortico-limbic networks. The medial prefrontal cortex (mPFC) sub-regions (prelimbic and infralimbic) make distinct contributions to drug-seeking behaviors. The prelimbic (PrL) facilitates drug seeking, while the infralimbic (IFrL) prevents it. Widespread projections connect the cerebellum to the mPFC, for this reason we should consider its participation in to drug addiction. Recently, it has been found two cerebellar hallmark signatures of conditioned preference for cocaine: an increase in cFOS expression in cells at the apex of the granule cell layer, and stronger expression of perineuronal nets (PNNs) surrounding Golgi interneurons in the same region of the cerebellar vermis. Considering those prefrontal-cerebellum projections, we suggest that there might be two specific functional pathways that connect the mPFC to cerebellum, one to promote drug-seeking (PrL– ventral cerebellar cortex) and another one to extinguish it (IFrL- dorsal cerebellar cortex). In the present study we aim to investigate what happen after a dorsal cerebellar lesion of lobule VIII on the PrL plasticity through a preference-conditioning paradigm in order to corroborate our hypothesis that these regions will not be connected functionally. We found that a lesion in the dorsal region of the cerebellar cortex promotes preference towards the odour associated with cocaine but the acquisition of a drug-related memory seems not affect to the intensity and number of PNNs expressed in the PrL. However, we find higher cFOS levels in the PrL cortex after the cerebellar lesion, which was not expected.