TY - JOUR
T1 - Age- and Sex-Related Characteristics of Tonic Gaba Currents in the Rat Substantia Nigra Pars Reticulata
AU - Chudomel, O.
AU - Hasson, H.
AU - Bojar, M.
AU - Moshé, S. L.
AU - Galanopoulou, A. S.
N1 - Funding Information:
The authors acknowledge the Grant support by NIH NINDS Grants NS020253, NS045243, NS058303, NS062947, NS078333, grants from the International Rett Syndrome Foundation, PACE, Heffer Family Foundation, Autism Speaks, Citizens United for Research in Epilepsy (CURE), Department of Defense, and GAČR 309/08/H079. SLM is the Charles Frost Chair in Neurosurgery and Neurology.
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age- and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.
AB - Previous studies have shown that the pharmacologic effects of GABAergic drugs and the postsynaptic phasic GABAAergic inhibitory responses in the anterior part of the rat substantia nigra pars reticulata (SNRA) are age- and sex-specific. Here, we investigate whether there are age- and sex-related differences in the expression of the δ GABAA receptor (GABAAR) subunit and GABAAR mediated tonic currents. We have used δ-specific immunochemistry and whole cell patch clamp to study GABAAR mediated tonic currents in the SNRA of male and female postnatal day (PN) PN5-9, PN11-16, and PN25-32 rats. We observed age-related decline, but no sex-specific changes, in bicuculline (BIM) sensitive GABAAR tonic current density, which correlated with the decline in δ subunit in the SNRA between PN15 and 30. Furthermore, we show that the GABAAR tonic currents can be modified by muscimol (GABAAR agonist; partial GABACR agonist), THIP (4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol: α4β3δ GABAARs agonist and GABACR antagonist), and zolpidem (α1-subunit selective GABAAR agonist) in age- and sex-dependent manner specific for each drug. We propose that the emergence of the GABAAR-sensitive anticonvulsant effects of the rat SNRA during development may depend upon the developmental decline in tonic GABAergic inhibition of the activity of rat SNRA neurons, although other sex-specific factors are also involved.
KW - Development
KW - GABA agonists
KW - Patch clamp
KW - Sex differences
KW - Substantia nigra pars reticulata
KW - Tonic inhibition
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U2 - 10.1007/s11064-015-1523-3
DO - 10.1007/s11064-015-1523-3
M3 - Article
C2 - 25645446
AN - SCOPUS:84939975788
SN - 0364-3190
VL - 40
SP - 747
EP - 757
JO - Neurochemical Research
JF - Neurochemical Research
IS - 4
ER -