Perinatal protein malnutrition facilitates morphine cross-sensitization to cocaine in adult rats

PERONDI M.C.; TORTONI G.; VALDOMERO A.; CUADRA G.R.

Huerta Grande, Córdoba

Congreso; XXIX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2014

Sociedad Argentina de Investigación en Neurociencias (SAN)

In order to study the influence of early nutritional insult on the development of cross-sensitization to the rewarding properties of cocaine in adult rats, different groups of control (C) and protein deprived (D) rats were pretreated twice a day for three days with escalating doses of morphine (5, 10 and 20 mg/ kg, s.c.). After the development of sensitization, the rewarding effect of cocaine was evaluated in D- and C-rats in a Conditioned Place Preference (CPP) paradigm. Dose-response curves to cocaine (3, 5, 7.5, 10 and 15 mg/kg i.p.) evidenced a conditioning effect in D-rats with doses of 5, 7.5 and 10 mg/kg, whereas no effect was observed with the lowest dose used (3 mg/kg). In C-rats, cocaine elicited place preference only with the higher dose of cocaine (15 mg/kg). Moreover, when the animals where pretreated twice a day for three days with increasing doses of morphine, only D-rats showed sensitization to rewarding properties with low doses of cocaine (5 and 7.5 mg/kg i.p.), which correlates with an over-expression of FosB in selective brain areas related to the rewarding circuit. Similar brain and plasma morphine / cocaine levels were previously observed in D- and C-rats, so pharmacokinetic alterations induced by early undernutrition might be ruled out. These results suggest that a deficient nutritional status during the gestational period may induce in adult subjects a lower threshold for developing a behavioral cross-sensitization to cocaine.