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The Journal of Neuroscience, February 11, 2009, 29(6):1755-1765; doi:10.1523/JNEUROSCI.3684-08.2009

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Cellular/Molecular
Changes in Expression and Function of Extrasynaptic GABA_A Receptors in the Rat Hippocampus during Pregnancy and after Delivery

Enrico Sanna,^1,2 Maria Cristina Mostallino,³ Luca Murru,¹ Mario Carta,¹ Giuseppe Talani,¹ Stefano Zucca,¹ Maria Luisa Mura,¹ Elisabetta Maciocco,³ and Giovanni Biggio^1,2,3

¹Department of Experimental Biology, Section of Neuroscience, and ²Center of Excellence for the "Neurobiology of Dependence," University of Cagliari, and ³National Research Council, Institute of Neuroscience, 09123 Cagliari, Italy

Correspondence should be addressed to Dr. Enrico Sanna, Department of Experimental Biology, Section of Neuroscience, University of Cagliari, Cittadella Universitaria, 09123 Cagliari, Italy. Email: esanna{at}unica.it

Pregnancy is associated with changes in mood and anxiety level as well as with marked hormonal fluctuations. Increases in the brain concentrations of neuroactive steroids during pregnancy in rats are accompanied by changes in expression of subunits of the GABA type A receptor (GABA_A-R) in the brain. Granule cells of the dentate gyrus (DGGCs) exhibit two components of inhibitory GABAergic transmission: a phasic component mediated by synaptic GABA_A-Rs, and a tonic component mediated by extrasynaptic GABA_A-Rs. Recordings of GABAergic currents were obtained from hippocampal slices prepared from rats in estrus, at pregnancy day 15 (P15) or P19, or at 2 d after delivery. Exogenous GABA or 3,5-THP induced an increase in tonic current in DGGCs that was significantly greater at P19 than in estrus. Neither tonic nor phasic currents were affected by pregnancy in CA1 pyramidal cells. Immunohistochemical analysis revealed a marked increase in the abundance of the subunit of the GABA_A-R and a concomitant decrease in that of the ₂ subunit in the hippocampus at P19. Expression of the ₄ subunit did not change during pregnancy but was increased 2 d after delivery. Treatment of rats from P12 to P18 with the 5-reductase inhibitor finasteride prevented the changes in tonic current and in and ₂ subunit expression normally apparent at P19. These data suggest that the number of extrasynaptic GABA_A-Rs is increased in DGGCs during late pregnancy as a consequence of the associated marked fluctuations in the brain levels of neuroactive steroids.

Key words: GABA_A receptor ; subunit; pregnancy; delivery; 3-hydroxy-5-pregnan-20-one; dentate gyrus granule cells; tonic current

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Received Aug. 4, 2008; revised Sept. 9, 2008; accepted Dec. 20, 2008.

Correspondence should be addressed to Dr. Enrico Sanna, Department of Experimental Biology, Section of Neuroscience, University of Cagliari, Cittadella Universitaria, 09123 Cagliari, Italy. Email: esanna{at}unica.it

This article has been cited by other articles:

				J. Maguire, I. Ferando, C. Simonsen, and I. Mody Excitability Changes Related to GABAA Receptor Plasticity during Pregnancy J. Neurosci., July 29, 2009; 29(30): 9592 - 9601. [Abstract] [Full Text] [PDF]

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