Age- and sex-related characteristics of tonic GABA currents in the rat substantia nigra pars reticulata. 2015

O Chudomel, and H Hasson, and M Bojar, and S L Moshé, and A S Galanopoulou
Saul R. Korey Department of Neurology, Laboratory of Developmental Epilepsy Bronx, Albert Einstein College of Medicine, 1410 Pelham Pkwy South, Kennedy Rm 306, Bronx, NY, 10461, USA, ondrej.chudomel@gmail.com.

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.

UI MeSH Term Description Entries
D008297 Male Males
D009118 Muscimol A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies. Agarin,Pantherine
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D005260 Female Females
D005680 gamma-Aminobutyric Acid The most common inhibitory neurotransmitter in the central nervous system. 4-Aminobutyric Acid,GABA,4-Aminobutanoic Acid,Aminalon,Aminalone,Gammalon,Lithium GABA,gamma-Aminobutyric Acid, Calcium Salt (2:1),gamma-Aminobutyric Acid, Hydrochloride,gamma-Aminobutyric Acid, Monolithium Salt,gamma-Aminobutyric Acid, Monosodium Salt,gamma-Aminobutyric Acid, Zinc Salt (2:1),4 Aminobutanoic Acid,4 Aminobutyric Acid,Acid, Hydrochloride gamma-Aminobutyric,GABA, Lithium,Hydrochloride gamma-Aminobutyric Acid,gamma Aminobutyric Acid,gamma Aminobutyric Acid, Hydrochloride,gamma Aminobutyric Acid, Monolithium Salt,gamma Aminobutyric Acid, Monosodium Salt
D000077334 Zolpidem An imidazopyridine derivative and short-acting GABA-A receptor agonist that is used for the treatment of INSOMNIA. Imidazo(1,2-a)pyridine-3-acetamide, N,N,6-trimethyl-2-(4-methylphenyl)-,Ambien,Amsic,Bikalm,Dalparan,N,N,6-Trimethyl-2-(4-methylphenyl)imidazo(1,2a)pyridine-3-acetamide hemitartrate,SL 80.0750,SL-800750-23-N,Stilnoct,Stilnox,Zodormdura,Zoldem,Zolirin,Zolpi-Lich,Zolpidem 1A Pharma,Zolpidem AbZ,Zolpidem Hemitartrate,Zolpidem Tartrate,Zolpimist,Zolpinox,SL 800750 23 N,Zolpi Lich
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012737 Sex Factors Maleness or femaleness as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or effect of a circumstance. It is used with human or animal concepts but should be differentiated from SEX CHARACTERISTICS, anatomical or physiological manifestations of sex, and from SEX DISTRIBUTION, the number of males and females in given circumstances. Factor, Sex,Factors, Sex,Sex Factor
D013378 Substantia Nigra The black substance in the ventral midbrain or the nucleus of cells containing the black substance. These cells produce DOPAMINE, an important neurotransmitter in regulation of the sensorimotor system and mood. The dark colored MELANIN is a by-product of dopamine synthesis. Nigra, Substantia,Nigras, Substantia,Substantia Nigras

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