title: Neonatal estradiol exposure to female rats changes GABAAreceptor expression and function, and spatial learning during adulthood.
abstract: Exposure of female rats to estradiol during the perinatal period has profound effects on GABAergic neurotransmission that are crucial to establish sexually dimorphic brain characteristics. We previously showed that neonatal β-estradiol 3-benzoate (EB) treatment decreases brain concentrations of the neurosteroid allopregnanolone, a potent positive modulator of extrasynaptic GABAAreceptors (GABAAR). We thus evaluated whether neonatal EB treatment affects GABAAR expression and function in the hippocampus of adult female rats. Neonatal EB administration increased the expression of extrasynaptic α4/δ subunit-containing GABAARs and the modulatory action of THIP on tonic currents mediated by these receptors. The same treatment decreased the expression of synaptic α1/α4/γ2 subunit-containing receptors, as well as phasic currents. These effects of neonatal EB treatment are not related to ambient allopregnanolone concentrations per se, given that vehicle-treated rats in diestrus, which have opposite neurosteroid levels than EB-treated rats, show similar changes in GABAARs. Rather, these changes may represent a compensatory mechanism to counteract the long-term reduction in allopregnanolone concentrations, induced by neonatal EB. Given that both α4/δ receptors and allopregnanolone are involved in memory consolidation, we evaluated whether neonatal EB treatment alters performance in the Morris water maze test during adulthood. Neonatal EB treatment decreased the latency and the cumulative search error to reach the platform, as well as thigmotaxis, suggesting improved learning, and also enhanced memory performance during the probe trial. These enduring changes in GABAAR plasticity may be relevant for the regulation of neuronal excitability in the hippocampus and for the etiology of psychiatric disorders that originate in development and show sex differences.
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Andrea
authors: A
authors: Locci
authors: Neuroscience Institute, National Research Council of Italy (CNR), Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Patrizia
authors: P
authors: Porcu
authors: Neuroscience Institute, National Research Council of Italy (CNR), Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Giuseppe
authors: G
authors: Talani
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Francesca
authors: F
authors: Santoru
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Roberta
authors: R
authors: Berretti
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Elisa
authors: E
authors: Giunti
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Valentina
authors: V
authors: Licheri
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy; Neuroscience Institute, National Research Council of Italy (CNR), Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy.
authors: Enrico
authors: E
authors: Sanna
authors: Department of Life and Environment Sciences, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy; Neuroscience Institute, National Research Council of Italy (CNR), Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy. Electronic address: aconcas@unica.it.
authors: Alessandra
authors: A
authors: Concas
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011280:Pregnanolone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism* / Q000502:physiology*; D012727:Sex Characteristics; D065853:Spatial Learning / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; C074283:estradiol 3-benzoate; D004958:Estradiol; D011280:Pregnanolone
keywords: Allopregnanolone; GABA(A) receptor; Hippocampus; Neonatal estradiol; Spatial learning; Tonic current