Increased negative affect when combining early-life maternal deprivation with adolescent, but not adult, cocaine exposure in male rats: regulation of hippocampal FADD.

RATIONALE: Besides early drug initiation during adolescence, another vulnerability factor associated with increased risk for substance abuse later in life is early-life stress. One way of assessing such combined risk is by evaluating the emergence of increased negative affect during withdrawal (i.e., linked to persistence in drug seeking).

OBJECTIVES: To compare the impact of maternal deprivation with cocaine exposure at different ages on affective-like behavior and hippocampal neuroplasticity regulation.

METHODS: Maternal deprivation was performed in whole-litters of Sprague-Dawley rats (24 h, PND 9-10). Cocaine (15 mg/kg, 7 days, i.p.) was administered in adolescence (PND 33-39) or adulthood (PND 64-70). Changes in affective-like behavior were assessed by diverse tests across time (forced-swim, open field, novelty-suppressed feeding, sucrose preference). Hippocampal multifunctional FADD protein (balance between cell death and plasticity) was evaluated by Western blot.

RESULTS: Exposing rats to either maternal deprivation or adolescent cocaine did not modulate affective-like behavior immediately during adolescence, but increased negative affect in adulthood. Maternal deprivation combined with adolescent cocaine advanced the negative impact to adolescence. Adult cocaine exposure alone and/or in combination with maternal deprivation did not induce any behavioral changes at the time-points analyzed. FADD regulation might participate in the neural adaptations taking place in the hippocampus in relation to the observed behavioral changes.

CONCLUSIONS: Adolescence is a more vulnerable period, as compared to adulthood, to the combined impact of cocaine and early maternal deprivation, thus suggesting that the accumulation of stress early in life can anticipate the negative behavioral outcome associated with drug consumption.