Abstract
GABAergic (γ-aminobutyric acid) transmission in the substantia nigra pars reticulata is critical for seizure control. We tested the hypothesis that there is a differential regional distribution and functionality of nigral GABA(A) receptor sites that is developmentally regulated. In adult rats, we determined the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid (ZAPA, a presumed agonist of the low-affinity GABA(A) receptor site), bicuculline (an antagonist of the low-affinity GABA(A) receptor site) and γ-vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or posterior substantia nigra pars reticulata. ZAPA infusions (8 μg) were anticonvulsant in anterior substantia nigra but proconvulsant in posterior substantia nigra. Bicuculline infusions (100 ng) were proconvulsant in anterior substantia nigra but ineffective in posterior substantia nigra. An anticonvulsant dose of γ-vinyI-GABA, when infused in anterior substantia nigra, was proconvulsant when infused in posterior substantia nigra. In 15 day old rats, the effects of ZAPA were biphasic: 2 μg was anticonvulsant while 8 μg was proconvulsant. There was no regional specificity. The data suggest that with maturation there is functional regional segregation of specific GABA(A) receptor subtypes involved in substantia nigra-mediated seizure control.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 167-173 |
| Number of pages | 7 |
| Journal | European Journal of Pharmacology |
| Volume | 309 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 8 1996 |
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Keywords
- Development
- GABA (γ-aminobutyric acid)
- GABA(A) receptor
- Rat
- Seizure
- Substantia nigra
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Pharmacology
Cite this
Developmental regulation of regional functionality of substantia nigra GABA(A) receptors involved in seizures. / Velisková, Jana; Velisek, Libor; Nunes, Magda L.; Moshe, Solomon L.
In: European Journal of Pharmacology, Vol. 309, No. 2, 08.08.1996, p. 167-173.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Developmental regulation of regional functionality of substantia nigra GABA(A) receptors involved in seizures
AU - Velisková, Jana
AU - Velisek, Libor
AU - Nunes, Magda L.
AU - Moshe, Solomon L.
PY - 1996/8/8
Y1 - 1996/8/8
N2 - GABAergic (γ-aminobutyric acid) transmission in the substantia nigra pars reticulata is critical for seizure control. We tested the hypothesis that there is a differential regional distribution and functionality of nigral GABA(A) receptor sites that is developmentally regulated. In adult rats, we determined the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid (ZAPA, a presumed agonist of the low-affinity GABA(A) receptor site), bicuculline (an antagonist of the low-affinity GABA(A) receptor site) and γ-vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or posterior substantia nigra pars reticulata. ZAPA infusions (8 μg) were anticonvulsant in anterior substantia nigra but proconvulsant in posterior substantia nigra. Bicuculline infusions (100 ng) were proconvulsant in anterior substantia nigra but ineffective in posterior substantia nigra. An anticonvulsant dose of γ-vinyI-GABA, when infused in anterior substantia nigra, was proconvulsant when infused in posterior substantia nigra. In 15 day old rats, the effects of ZAPA were biphasic: 2 μg was anticonvulsant while 8 μg was proconvulsant. There was no regional specificity. The data suggest that with maturation there is functional regional segregation of specific GABA(A) receptor subtypes involved in substantia nigra-mediated seizure control.
AB - GABAergic (γ-aminobutyric acid) transmission in the substantia nigra pars reticulata is critical for seizure control. We tested the hypothesis that there is a differential regional distribution and functionality of nigral GABA(A) receptor sites that is developmentally regulated. In adult rats, we determined the effects on flurothyl seizures of (Z)-3-[(aminoiminomethyl)thio]prop-2-enoic acid (ZAPA, a presumed agonist of the low-affinity GABA(A) receptor site), bicuculline (an antagonist of the low-affinity GABA(A) receptor site) and γ-vinyl-GABA (a GABA-transaminase inhibitor), infused bilaterally in anterior or posterior substantia nigra pars reticulata. ZAPA infusions (8 μg) were anticonvulsant in anterior substantia nigra but proconvulsant in posterior substantia nigra. Bicuculline infusions (100 ng) were proconvulsant in anterior substantia nigra but ineffective in posterior substantia nigra. An anticonvulsant dose of γ-vinyI-GABA, when infused in anterior substantia nigra, was proconvulsant when infused in posterior substantia nigra. In 15 day old rats, the effects of ZAPA were biphasic: 2 μg was anticonvulsant while 8 μg was proconvulsant. There was no regional specificity. The data suggest that with maturation there is functional regional segregation of specific GABA(A) receptor subtypes involved in substantia nigra-mediated seizure control.
KW - Development
KW - GABA (γ-aminobutyric acid)
KW - GABA(A) receptor
KW - Rat
KW - Seizure
KW - Substantia nigra
UR - http://www.scopus.com/inward/record.url?scp=0030575531&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030575531&partnerID=8YFLogxK
U2 - 10.1016/0014-2999(96)00341-X
DO - 10.1016/0014-2999(96)00341-X
M3 - Article
C2 - 8874135
AN - SCOPUS:0030575531
VL - 309
SP - 167
EP - 173
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2
ER -