Increased negative affect when combining early-life maternal deprivation with adolescent, but not adult, cocaine exposure in male rats: regulation of hippocampal FADD
Psychopharmacology. 2020-10-27; 238(2): 411-420
DOI: 10.1007/s00213-020-05689-4
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Bis-Humbert C(1)(2), García-Cabrerizo R(1)(2)(3), García-Fuster MJ(4)(5).
Author information:
(1)IUNICS, University of the Balearic Islands, Cra. de Valldemossa km 7.5,
E-07122, Palma, Spain.
(2)Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
(3)APC Microbiome Ireland, University College Cork, Cork, Ireland.
(4)IUNICS, University of the Balearic Islands, Cra. de Valldemossa km 7.5,
E-07122, Palma, Spain. .
(5)Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
.
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.