Nicotine. Behavioral analysis to evaluate the rewarding properties of nicotine in zebrafish. Epigenetic.

R. BERNABEU

Cordoba, Argentina

Simposio; NEUROBIOLOGY OF DRUG ADDICTION SAN IBRO LARC Course and ISN Small Conference (ISN-CC); 2018

Nicotine is the principal addictive component of tobacco that drives continued use despite users´ knowledge of its harmful consequences. We evaluated the reinforcing effects of nicotine through the use of a Pavlovian conditioning test called conditioned place preference (CPP) as a method to determine the preference or rewarding properties of nicotine. We investigated at the behavioral, pharmacological and neurochemical level, the rewarding and relapsing effects of nicotine, as well as the individual vulnerability to the drug using the experimental animal model of zebrafish. To this end, we are designing new behavioral tests, in order to better characterize the rewarding properties of nicotine. We are also interested in describing epigenetic factors involved in the stages of reward and relapse in drug addiction, since emerging evidence suggests that epigenetic alterations to the genome, including DNA methylation and histone modification, are important mechanisms underlying addiction to psychostimulants. Recently, we identified three epigenetic molecules (CREB, HDAC2 and MeCP2) that participate in the establishment of nicotine CPP. In addition, we demonstrated that a histone deacetylase inhibitor (HDAC), phenylbutyrate, was able to drastically reduce the preference for nicotine. At present, we are analyzing if other stimulants can reduce nicotine preference and we are evaluating factors that can determine the individual vulnerability to nicotine consumption.