title: Prenatal ethanol exposure alters met-enkephalin expression in brain regions related with reinforcement: possible mechanism for ethanol consumption in offspring.
abstract: The endogenous opioid system is involved in ethanol reinforcement. Ethanol-induced changes in opioidergic transmission have been extensively studied in adult organisms. However, the impact of ethanol exposure at low or moderate doses during early ontogeny has been barely explored. We investigated the effect of prenatal ethanol exposure on alcohol intake and Methionine-enkephalin (Met-enk) content in rat offspring. Met-enk content was assessed in the ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. Pregnant rats were treated with ethanol (2g/kg) or water during GDs 17-20. At PDs 14 and 15, preweanlings were evaluated in an intake test (5% and 10% ethanol, or water). Met-enk content in brain regions of infants prenatally exposed to ethanol was quantitated by radioimmunoassay. Ethanol consumption was facilitated by prenatal experience with the drug, particularly in females. Met-enk content in mesocorticolimbic regions - PFC and NAcc - was increased as a consequence of prenatal exposure to ethanol. Conversely, Met-enk levels in the VTA were reduced by prenatal ethanol manipulation. Prenatal ethanol also increased peptide levels in the medial-posterior zone of the CP, and strongly augmented Met-enk content in the hippocampus and hypothalamus. These findings show that prenatal ethanol exposure stimulates consumption of the drug in infant rats, and induces selective changes in Met-enk levels in regions of the mesocorticolimbic and nigrostriatal systems, the hypothalamus and hippocampus. Our results support the role of mesocorticolimbic enkephalins in ethanol reinforcement in offspring, as has been reported in adults.
authors.affiliation: Instituto de Investigación Médica M. y M. Ferreyra, INIMEC-CONICET, Universidad Nacional de Córdoba, Córdoba, C.P. 5000, Argentina; Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, C.P. 5000, Argentina. Electronic address: pabate@immf.uncor.edu.
authors.forename: P
authors.initials: P
authors.lastname: Abate
authors.affiliation: Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., Mexico.
authors.forename: K
authors.initials: K
authors.lastname: Hernández-Fonseca
authors.affiliation: Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., Mexico.
authors.forename: A C
authors.initials: AC
authors.lastname: Reyes-Guzmán
authors.affiliation: Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., Mexico.
authors.forename: I G
authors.initials: IG
authors.lastname: Barbosa-Luna
authors.affiliation: Departamento de Neuroquímica, Subdirección de Investigaciones Clínicas, Instituto Nacional de Psiquiatría Ramón de la Fuente, Calzada México Xochimilco 101, Col. San Lorenzo Huipulco, 14370 México D.F., Mexico. Electronic address: ubach@imp.edu.mx.
authors.forename: M
authors.initials: M
authors.lastname: Méndez
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000097:blood; D004744:Enkephalin, Methionine / Q000378:metabolism*; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000473:pathology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D004744:Enkephalin, Methionine
keywords: Enkephalins; Ethanol; Offspring; Ontogeny; Opioid peptides; Reinforcement