Perinatal protein malnutrition enhances rewarding cocaine properties in adult rats

The rewarding properties of cocaine were assessed in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 40 days of age (deprived rats), as compared with well-nourished animals (control rats) using the conditioned place preference paradigm. Dose-response curves to cocaine (3, 5, 10, 15, 30, 45 or 60 mg/kg i.p.) revealed in deprived rats a conditioning effect with doses of 5 and 10mg/kg; doses of 15 and 30 mg/kg did not show any conditioning place preference and doses of 45 and 60 mg/kg revealed a significant aversive effect. In control rats, cocaine elicited place preference with doses of 10, 15 and 30 mg/kg, whereas 45 and 60 mg/kg did not show either conditioning or aversive effects. Furthermore, sensitization to the conditioning effect of cocaine was obtained in deprived animals with a low dosage of cocaine, that was ineffective in controls (5 mg/kg/day for 10 days). Related to the higher rewarding effects, sensitized deprived rats showed a selective and significant increase in FosB expression in nucleus accumbens (core and shell) and basolateral amygdala, brain areas related to the rewarding neuronal circuits. These results suggest that a deficient nutritional status during early life may induce in adult subjects an increased responsiveness to behavioral effects of cocaine and/or enhanced its reinforcement properties.