SENSITIZATION-DEPENDENT NICOTINE PLACE PREFERENCE IN THE ADULT ZEBRAFISH.

PISERA FUSTER ANTONELLA; FAILLACE MARIA PAULA; BERNABEU, RAMON O

Congreso; Reunion conjunta de sociedades de biociencia; 2017

Tobacco smoking is a riskfactor for subsequent cocaine abuse, but the neural substrates underlying thisrisk remain unknown. Locomotor sensitization is a robust and readily assayedeffect of psychostimulants, while conditioning place preference (CPP) is a morenaturalistic model of addictive behavior. To understand the biological basis of nicotine induce reward, weanalyzed first sensitization to nicotine and/or cocaine in zebrafish by exposinganimals five days (20 min-day) to either drug followed by five days ofabstinence before a challenge dose. We tested next if sensitized zebrafish caninduce nicotine place preference using a biased design. Locomotor sensitizationwas increased by 103% with nicotine and 166% with cocaine. In addition, both nicotineand cocaine previously sensitized animals showed positive nicotine CPP, using anicotine dose that cannot generate CPP by it self. Zebrafish sensitization and CPPwas corroborated by behavioral analysis of several indicators of drug exposureand preference, such as locomotor activity, time spent in the upper-zone, timespent in the drug-paired side, number of entries to the drug-paired side, anddistance traveled. The behavioral results obtained were also accompanied withchances in the expression of some molecular markers, measured by qPCR, such asnicotine receptors subunits, DAT and Pitx3, which are associated with drugreward. These results from zebrafish strongly suggest that repeated exposure tonicotine and/or cocaine induce sensitization by increasing the vulnerabilityand facilitating the rewarding properties of nicotine, although the dose of nicotine is not sufficient to induce seeking behavior per se. The behavioral characterization of these responses inzebrafish may be the first important step towards establishing this species asa tool for the analysis of molecular and neurobiological mechanisms underlyinghuman drug seeking behavior.