Perinatal protein deprivation facilitates morphine cross-sensitization to cocaine and enhances Delta FosB expression in adult rats

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

Congreso; XVII Congreso Latinoamericano de Nutrición de la Sociedad Latinoamericana de Nutrición; 2015

SLAN - Sociedad Latinoamericana de Nutrición

Perinatal protein deprivation produces dramatic damage tothe developing brain. The present study aimed to investigatewhether early nutritional insult affects the development ofbehavioral cross-sensitization to rewarding properties of cocainein adult rats. Different groups of control (C) and proteindeprived (D) rats were treated with saline (1 ml/kg, s.c.) orescalating doses of morphine (5, 10 and 20 mg/kg, s.c.), twicea day. Seventy-two hours after that sensitization phase, rewardingproperties 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 withdoses of 5, 7.5 and 10 mg/kg of cocaine was observed in Drats pretreated with saline; such effect was not observed withthe lowest dose used (3 mg/kg). In saline pretreated C rats,conditioning effect was only pointed out with high doses ofcocaine (10 and 15 mg/kg). Furthermore, when animals werepretreated with morphine, only D rats developed sensitizationto the conditioning effect with low doses of cocaine (5 and7.5 mg/kg). Under our experimental conditions, C rats did notshow cross-sensitization. Moreover, sensitized D rats conditionedwith 5 mg/kg of cocaine showed a selective and significantincrease in ΔFosB expression in nucleus accumbens coreand shell, basolateral amygdala and cingulated, prelimbic andinfralimbic cortex, areas related to rewarding brain circuits. Werule out the possibility that pharmacokinetic changes inducedby undernutrition may affect drug availability, since we formerlyfound similar brain and plasma morphine / cocaine levels inboth C and D groups. These results suggest that a deficientnutritional status during the perinatal period may induce a lowerthreshold for developing a behavioral cross-sensitization tococaine in adult subjects.