1 Departamento de Farmacología, IFEC (CONICET) - Facultad de Ciencias Químicas - Universidad Nacional de Córdoba. Córdoba, Argentina.
Perinatal protein deprivation produces dramatic damage to the developing brain. The present study aimed to investigate whether early nutritional insult affects the development of behavioral cross-sensitization to rewarding properties of cocaine in adult rats. Different groups of control (C) and protein deprived (D) rats were treated with saline (1 ml/kg, s.c.) or escalating doses of morphine (5, 10 and 20 mg/kg, s.c.), twice a day. Seventy-two hours after that sensitization phase, rewarding properties of cocaine (3, 5, 7.5, 10 and 15 mg/kg, i.p.) were assessed in a Conditioned Place Preference (CPP) paradigm in both C and D animals. The conditioning effect with doses of 5, 7.5 and 10 mg/kg of cocaine was observed in D rats pretreated with saline; such effect was not observed with the lowest dose used (3 mg/kg). In saline pretreated C rats, conditioning effect was only pointed out with high doses of cocaine (10 and 15 mg/kg). Furthermore, when animals were pretreated with morphine, only D rats developed sensitization to the conditioning effect with low doses of cocaine (5 and 7.5 mg/kg). Under our experimental conditions, C rats did not show cross-sensitization. Moreover, sensitized D rats conditioned with 5 mg/kg of cocaine showed a selective and significant increase in ΔFosB expression in nucleus accumbens core and shell, basolateral amygdala and cingulated, prelimbic and infralimbic cortex, areas related to rewarding brain circuits. We rule out the possibility that pharmacokinetic changes induced by undernutrition may affect drug availability, since we formerly found similar brain and plasma morphine / cocaine levels in both C and D groups. These results suggest that a deficient nutritional status during the perinatal period may induce a lower threshold for developing a behavioral cross-sensitization to cocaine in adult subjects.