Neural correlates of cocaine-induced conditioned place preference in the posterior cerebellar cortex

Olga Rodríguez-Borillo; Lorena Roselló-Jiménez; Julian Guarque-Chabrera; María Palau-Batet; Isis Gil-Miravet; Raúl Pastor; Marta Miquel; Laura Font

doi:10.3389/fnbeh.2023.1174189

Neural correlates of cocaine-induced conditioned place preference in the posterior cerebellar cortex

Front Behav Neurosci. 2023 Apr 26:17:1174189. doi: 10.3389/fnbeh.2023.1174189. eCollection 2023.

Authors

Olga Rodríguez-Borillo¹, Lorena Roselló-Jiménez¹, Julian Guarque-Chabrera^{1

2}, María Palau-Batet¹, Isis Gil-Miravet³, Raúl Pastor¹, Marta Miquel^{1

2}, Laura Font¹

Affiliations

¹ Área de Psicobiología, Universitat Jaume I, Castellón de la Plana, Spain.
² Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, United States.
³ Unitat Predepartamental de Medicina, Universitat Jaume I, Castellón de la Plana, Spain.

Abstract

Introduction: Addictive drugs are potent neuropharmacological agents capable of inducing long-lasting changes in learning and memory neurocircuitry. With repeated use, contexts and cues associated with consumption can acquire motivational and reinforcing properties of abused drugs, triggering drug craving and relapse. Neuroplasticity underlying drug-induced memories takes place in prefrontal-limbic-striatal networks. Recent evidence suggests that the cerebellum is also involved in the circuitry responsible for drug-induced conditioning. In rodents, preference for cocaine-associated olfactory cues has been shown to correlate with increased activity at the apical part of the granular cell layer in the posterior vermis (lobules VIII and IX). It is important to determine if the cerebellum's role in drug conditioning is a general phenomenon or is limited to a particular sensory modality.

Methods: The present study evaluated the role of the posterior cerebellum (lobules VIII and IX), together with the medial prefrontal cortex (mPFC), ventral tegmental area (VTA), and nucleus accumbens (NAc) using a cocaine-induced conditioned place preference procedure with tactile cues. Cocaine CPP was tested using ascending (3, 6, 12, and 24 mg/kg) doses of cocaine in mice.

Results: Compared to control groups (Unpaired and Saline animals), Paired mice were able to show a preference for the cues associated with cocaine. Increased activation (cFos expression) of the posterior cerebellum was found in cocaine CPP groups and showed a positive correlation with CPP levels. Such increases in cFos activity in the posterior cerebellum significantly correlated with cFos expression in the mPFC.

Discussion: Our data suggest that the dorsal region of the cerebellum could be an important part of the network that mediates cocaine-conditioned behavior.

Keywords: VTA; addiction; cFos; cerebellum; cocaine; conditioned place preference (CPP); mPFC; nucleus accumbens.

Grants and funding

This research was supported by PGC2018-095980-B-I00 funded by the Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe.” Grant Pla de Promoció de la Investigació UJI-B2021-28 and the Conselleria de Innovación, Universidades, Ciencia y Sociedad Digital Grant Generalitat Valenciana-AICO (2019/202 and 2021/215). OR-B was supported by Pre-doctoral fellowship Pla de Promoció de la Investigació UJI PREDOC/2019/35.