title: Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.
abstract: Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure.
authors.affiliation: Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET-Universidad Nacional de Córdoba), Friuli 2434, Córdoba C.P. 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Enfermera Gordillo s/n, Córdoba C.P. 5000, Argentina.
authors.forename: M C
authors.initials: MC
authors.lastname: Fabio
authors.affiliation: Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET-Universidad Nacional de Córdoba), Friuli 2434, Córdoba C.P. 5000, Argentina.
authors.forename: L M
authors.initials: LM
authors.lastname: Vivas
authors.affiliation: Instituto de Investigación Médica M. y M. Ferreyra (INIMEC - CONICET-Universidad Nacional de Córdoba), Friuli 2434, Córdoba C.P. 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Enfermera Gordillo s/n, Córdoba C.P. 5000, Argentina. Electronic address: rpautassi@gmail.com.
authors.forename: R M
authors.initials: RM
authors.lastname: Pautassi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: Fos; adolescent; dopamine; mesocorticolimbic pathway; prenatal ethanol; rat