Ethanol and nicotine interaction along ontogeny: changes in self-administration parameters and gene expression in the mesolimbic system

Abstract

Evidence suggests that previous or simultaneous exposure to ethanol enhances the vulnerability to nicotine abuse and addiction, similarly, the exposure to nicotine increases the vulnerability to ethanol. However the mechanisms involved in this interaction is not clearly understood. Adolescence is a age period of great risk of drug abuse, thus consumption of ethanol or tobacco at this age might increase the risk to addiction over the ontogeny. Although the primary mechanisms of action of nicotine and ethanol are different both substances alter the dopaminergic transmission in the mesolimbic system. Our hypothesis is that the exposure to ethanol or nicotine during adolescence cause similar neuroplasticities in this system that could increase the motivation to nicotine and ethanol respectively. The aim of the present study is to investigate: a) whether the previous exposure to ethanol increases the motivation and consume of nicotine; b) the previous exposure to nicotine increases the motivation and consume of ethanol; c) whether a priming injection of ethanol can reinstate the self-administration of nicotine and vice-versa; d) changes in gene expression (BDNF, TrK-B, CRH, CRH1, dynorphin, u opiod receptor, and NPY) in the mesocorticolimbic system following ethanol and nicotine repeated administration. To this end we will use the operant oral or intravenous self-administration model respectively for ethanol and nicotine to evaluate behavioral changes and RT-PCR to evaluate changes in gene expression. (AU)