title: Neonatal finasteride administration decreases dopamine release in nucleus accumbens after alcohol and food presentation in adult male rats.
abstract: Endogenous levels of the neurosteroid (NS) allopregnanolone (AlloP) during neonatal stages are crucial for the correct development of the central nervous system (CNS). In a recent work we reported that the neonatal administration of AlloP or finasteride (Finas), an inhibitor of the enzyme 5α-reductase needed for AlloP synthesis, altered the voluntary consumption of ethanol and the ventrostriatal dopamine (DA) levels in adulthood, suggesting that neonatal NS manipulations can increase alcohol abuse vulnerability in adulthood. Moreover, other authors have associated neonatal NS alterations with diverse dopaminergic (DAergic) alterations. Thus, the aim of the present work is to analyse if manipulations of neonatal AlloP alter the DAergic response in the nucleus accumbens (NAcc) during alcohol intake in rats. We administered AlloP or Finas from postnatal day (PND) 5 to PND9. At PND98, we measured alcohol consumption using a two-bottle free-choice model (ethanol 10% (v/v)+glucose 3% (w/v), and glucose 3% (w/v)) for 12 days. On the last day of consumption, we measured the DA and 3,4-dihydroxyphenylacetic acid (DOPAC) release in NAcc in response to ethanol intake. The samples were obtained by means of in vivo microdialysis in freely moving rats, and DA and DOPAC levels were determined by means of high-performance liquid chromatography analysis (HPLC). The results revealed that neonatal Finas increased ethanol consumption in some days of the consumption phase, and decreased the DA release in the NAcc in response to solutions (ethanol+glucose) and food presentation. Taken together, these results suggest that neonatal NS alterations can affect alcohol rewarding properties.
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Llidó
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Bartolomé
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Sònia
authors.initials: S
authors.lastname: Darbra
authors.affiliation: Departament de Psicobiologia i Metodologia de les Ciències de la Salut, Institut de Neurociències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. Electronic address: marc.pallares@uab.cat.
authors.forename: Marc
authors.initials: M
authors.lastname: Pallarès
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000494:pharmacology; D058891:5-alpha Reductase Inhibitors / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002491:Central Nervous System Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D000431:Ethanol / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D005502:Food; D005947:Glucose / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000254:growth & development*; D017208:Rats, Wistar; D012201:Reward
chemical_list: D058891:5-alpha Reductase Inhibitors; D002491:Central Nervous System Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol; D018120:Finasteride; D005947:Glucose; D004298:Dopamine
keywords: Allopregnanolone; Dopamine; Ethanol consumption; Finasteride; Microdialysis; Nucleus accumbens