Plenary Lecture

Plenary Lecture

Influence of Repeated Exposure to Caffeine on Dopamine Transmission: Preclinical Evidence and Possible Implications

Dr. Nicola Simola
Department of Toxicology
University of Cagliari
Via Ospedale 72, I-09124, Cagliari

Abstract: Caffeine is one of the most popular psychostimulants in the world and is extensively consumed by both young and adult population. A large body of evidence demonstrates the existence of striking differences between caffeine and other psychostimulants abused by humans, like amphetamines of cocaine. For example, as compared to such substances, caffeine displays weaker rewarding and reinforcing effects. On these bases, and in light of the fact that caffeine exerts very negligible adverse effects, caffeine consumption is usually envisioned as a “safe habit”. In spite of this, however, a wealth of preclinical research has disclosed the capability of caffeine to modulate dopamine transmission in the brain, which plays a pivotal role in addiction phenomena. Together, these pieces of evidence have raised the possibility that caffeine consumption, although harmless by itself, could represent a factor capable of promoting the instatement of an addiction towards other psychoactive substances as well as of precipitating an existing addictive behaviour. In our laboratory the interactions between caffeine and the dopaminergic system have been investigated in a preclinical model of long-term caffeine administration. The results obtained indicate that, in the rat, repeated exposure to caffeine engenders a persistent hyperfunctionality of dopamine transmission in the striatum. In particular, it was observed that subchronic-intermittent caffeine elicited sensitization to its motor stimulant effects, indicative of the occurrence of neuroplastic changes in dopaminergic transmission. Such a sensitization was found to be paired with a decrease in the levels of both the mRNA for adenosine A2A receptors, which deeply interact with dopamine receptors, and the mRNA for the early gene zif-268, the latter being indicative of persistent modifications in the dopamine receptors signalling pathway. Furthermore, rats sensitized to caffeine displayed cross motor sensitization to amphetamine, increase in the expression of zif-268 mRNA, and an elevation in high-affinity dopamine D2 receptors (D2High). Taken together, these findings demonstrate that prolonged exposure to caffeine leads to neuroadaptations involving striatal dopaminergic transmission and corroborate the hypothesis that caffeine consumption may be a risk factor for addictive behaviours.

Brief Biography of the Speaker:
Dr. Simola received his M. S. Degree in Pharmaceutical Chemistry and Technology and his Ph. D. Degree in Pharmacology of Drug Abuse from the University of Cagliari, Italy. Currently, Dr. Simola performs his research activity at the Department of Toxicology of the University of Cagliari, having also spent a period as a visiting research fellow at the Institute for Neuroscience of the University of Texas at Austin, U.S.A. (2007-2009). Dr. Simola’s research involves the study and development of new therapeutic agents to be used in the treatment of Parkinson’s disease, focusing on adenosine receptor antagonists and metabolic enhancers, the development of new preclinical models of early-stage Parkinson’s disease, and the study of the interactions between caffeine and other recreational psychostimulants bearing addiciton potential. This research activity is carried out in collaboration with Universities and Research Centers in Italy and abroad. Dr. Simola is author of several articles on caffeine, Parkinson’s disease, neurodegeneartion and related topics which are published in International Scientific Journals, books and proceedings of scientific meetings.

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