title: Postnatal administration of allopregnanolone modifies glutamate release but not BDNF content in striatum samples of rats prenatally exposed to ethanol.
abstract: Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABAA receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to juvenile male rats (day 21 of age) on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8). Prenatal ethanol administration decreased the K(+)-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABAA receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.
authors: Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias de la Salud, Universidad de Mendoza, Paseo Dr. Emilio Descotte 720, 5500 Mendoza, Argentina ; Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Avenidad del Libertador 80, 5500 Mendoza, Argentina.
authors: Roberto
authors: R
authors: Yunes
authors: Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias de la Salud, Universidad de Mendoza, Paseo Dr. Emilio Descotte 720, 5500 Mendoza, Argentina.
authors: Cecilia R
authors: CR
authors: Estrella
authors: Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias de la Salud, Universidad de Mendoza, Paseo Dr. Emilio Descotte 720, 5500 Mendoza, Argentina ; Área de Farmacología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Avenidad del Libertador 80, 5500 Mendoza, Argentina.
authors: Sebastián
authors: S
authors: García
authors: Laboratorio de Neurobioquímica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Calle Sergio Livingstone Polhammer 1007, 8380492 Santiago de Chile, Chile.
authors: Hernán E
authors: HE
authors: Lara
authors: Instituto de Investigaciones Biomédicas (INBIOMED-IMBECU-CONICET), Facultad de Ciencias de la Salud, Universidad de Mendoza, Paseo Dr. Emilio Descotte 720, 5500 Mendoza, Argentina.
authors: Ricardo
authors: R
authors: Cabrera
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011963:Receptors, GABA-A; D000431:Ethanol; D018698:Glutamic Acid; D011280:Pregnanolone