CONICET | Buscador de Institutos y Recursos Humanos

Previous studies have indicated that neural changes induced by early nutritional insult cause an altered responseto pharmacological treatments, including addictive drugs. This study evaluates the influence of perinatal proteinmalnutrition in developing cross-sensitization to cocaine-induced rewarding effects in animals pre-exposed tomorphine.Different groups of well-nourished (C-rats) and protein-deprived animals (D-rats) were treated twice a day forthree days with increasing doses of morphine or with saline. After 3 days, the incentive motivational effects ofcocaine were assessed in a Conditioned Place Preference paradigm in both groups. In saline pre-treated animals,dose-response curves to cocaine revealed a conditioning effect in D-rats at doses of 5, 7.5 and 10 mg/kg, whilethis effect was observed in C-rats only with 10 and 15 mg/kg. Furthermore, when animals of both groups werepre-treated with escalating doses of morphine, cross-sensitization to the conditioning effect of cocaine waselicited only in D-rats with low doses of cocaine (5 and 7.5 mg/kg). In contrast, under the same experimentalconditions, C-rats show no cross-sensitization. To correlate this differential rewarding response with a molecularsubstrate linked to the behavioral changes observed after repeated drug exposure, ΔFosB expression was assessedin different brain regions. D-rats showed a significant increase in this transcription factor in the nucleus accumbens,amygdala and medial prefrontal cortex. These results demonstrated that perinatal protein deprivationfacilitates rewarding effects and the development of cross-sensitization to cocaine, which correlates with anupregulation of ΔFosB in brain areas related to the reward circuitry.