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E F Sperber

Publications and source records attributed to E F Sperber.

46 records · Page 3Linked to original sources
PubMed1989

Evidence for the involvement of nigral GABAA receptors in seizures of adult rats.

Several studies have implicated the substantia nigra GABAergic system in the mediation of seizures in adult rats. The present study examines whether the different GABA receptors (GABAA and GABAB), are preferentially involved in this GABAergic seizure suppression mechanism. Adult rats were intranigrally infused with muscimol (GABAA receptor agonist), bicuculline (GABAA receptor antagonist) or baclofen (GABAB receptor agonist) and were exposed to flurothyl seizures. Results indicated that while infusions of muscimol had an anticonvulsant effect, infusions of bicuculline had a proconvulsant effect. Baclofen infusions were found to have no effect on seizures. These findings suggest an involvement of the nigral GABAA receptors in the mediation of seizures in adult rats.

Animals↗
PubMed1989

Intranigral GABAergic drug effects on striatal dopamine activity.

Concentrations of striatal dopamine (DA), serotonin (5-HT) and their metabolites were measured following infusions of the GABAA receptor agonist, muscimol, or GABAA receptor antagonist, bicuculline, into the substantia nigra (SN) or areas dorsal to the SN in adult rats and 16-day-old rat pups. Results indicated that intranigral infusions of muscimol produced site-specific increases in the concentrations of striatal DA metabolites in adults, while in pups, intranigral muscimol infusions produced site-specific increases in the concentrations of striatal DA. Intranigral infusions of bicuculline had no effect on striatal DA or its metabolites in either age group. Neither GABAergic drug had any effect on striatal 5-HT or its metabolite. The data suggest that the effect of nigral GABAA agonist infusions on the activity of the nigrostriatal pathway is age-specific. The lack of opposing effects following the nigral infusion of a GABAA receptor antagonist indicates that the influences of GABAA agonists may be mediated by different mechanisms as a function of age.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Age-related changes of muscimol binding in the substantia nigra.

Receptor binding studies of the substantia nigra (SN) and cerebellum revealed two affinity sites for muscimol binding in the SN and cerebellum of adult and 16-day-old rats. Scatchard analysis revealed a paucity of high-affinity muscimol receptors in the SN of 16-day-old rat pups. These results suggest that the lack of anticonvulsant action of muscimol in the SN of 16-day-old rat pups may be due to the paucity of high-affinity muscimol receptors as compared to adult rats.

Aging↗
PubMed1988

Age-related differences in seizure susceptibility to flurothyl.

The purpose of the present study was to determine whether the susceptibility to seizures induced by inhalation of flurothyl ether (FE) varies with age. Adult rats and 16-day-old rat pups were tested in different sized chambers to also determine whether the size of the FE-test chamber influences seizure thresholds. Results indicate that pups developed age-specific seizure patterns; their seizure latency thresholds were shorter than those of adult animals. For both age-groups, seizure thresholds varied as a function of chamber size; the smaller the chamber the faster seizures occurred.

Age Factors↗
PubMed1987

Nigral infusions of muscimol or bicuculline facilitate seizures in developing rats.

The substantia nigra (SN) appears to be a crucial site involved in the modification of seizures. The aim of this study was to elucidate the role of the GABA nigral system in the expression of seizures by comparing the effects of multiple doses of a GABA agonist (muscimol) and a GABA antagonist (bicuculline methobromide) on the development of flurothyl seizures in 16-day-old rat pups. The drugs were infused bilaterally either in the SN or dorsal to the SN. An additional group of pups were infused with bicuculline in the corpus striatum. Results indicate that both drugs facilitated the development of seizures in a dose-related manner when infused into the SN. Infusions of muscimol dorsal to the SN had no effect on seizure latencies while infusions of bicuculline dorsal to SN or corpus striatum still increased the susceptibility of rat pups to seizures. The data suggest that only the effects of muscimol on seizures are specific for the SN and that early in life muscimol may exert its proconvulsant effects via a different receptor site or mechanism than bicuculline.

Animals↗
PubMed1987

Age-related changes in striatal dopamine activity following nigral muscimol infusions.

Microinfusions of muscimol into the substantia nigra pars reticulata produced marked increases in striatal dopamine (DA) utilization without affecting striatal DA concentration in adult rats. In contrast, muscimol increased striatal DA concentration and decreased DA utilization in 16-day-old rat pups. The striatal norepinephrine concentration was not altered in either group. Since previous studies have shown that similar infusions of muscimol are anticonvulsant in adults and proconvulsant in rat pups, our results suggest that the nigrostriatal pathway may play an important role in mediating the nigral effects on seizures.

Aging↗
PubMed1986

Age-related substantia nigra-mediated seizure facilitation.

We investigated the role of the GABAergic system of the substantia nigra in seizures of rat pups. Rat pups had bilateral cannulae implanted chronically either in the substantia nigra or 1.5 mm dorsal to it. At age 16 to 17 days, seizures were induced in the cannulated rats and naive (intact) controls by exposure to flurothyl following pretreatment with the GABA agonist, muscimol, or vehicle. Naive rats were the most resistant to flurothyl seizures. Bilateral nigral infusions of muscimol markedly facilitated the development of flurothyl seizures in a dose-response manner and differed significantly from the vehicle controls or rats infused with muscimol dorsally to the substantia nigra. In contrast, bilateral nigral muscimol infusions protected adult rats against the development of flurothyl seizures. Our data indicate that the effects of nigral GABA agonist infusions on seizures are age-dependent; the altered responsivity of the GABAergic nigral system in immature rats may be responsible in part for the increased seizure susceptibility of the developing central nervous system.

Animals↗
PubMedDate not supplied

Baclofen inhibits amygdala kindling in immature rats.

The possible effectiveness of systemic infusions of baclofen (a GABAB receptor agonist) in the modification of seizures in developing animals has not yet been established. In this report, we studied the effects of systemic baclofen infusions on amygdala kindling in 16-day-old rat pups. Baclofen suppressed the development of kindling without altering the local afterdischarge threshold. Moreover, baclofen suppressed the severity and duration of established kindled seizures and increased the intensity of postictal refractoriness. The data suggest that baclofen may be a useful antiepileptic agent in this age group.

Amygdala↗
PubMedDate not supplied

Age-dependent differences in the anticonvulsant effects of 2-amino-7-phosphono-heptanoic acid or ketamine infusions into the substantia nigra of rats.

Infusions of 2-amino-7-phosphonoheptanoic acid (AP7) or ketamine into the substantia nigra pars reticulata (SNPR) of adult rats increase the latency of onset to seizures induced by the convulsant ether flurothyl. Nigral infusions of AP7 or ketamine in concentrations up to 10 times greater than the adult dose are ineffective in 16-day-old rats. These results suggest that differences in seizure susceptibility between adult and immature rats may be related to differences in excitatory amino acid neurotransmission in the SN.

2-Amino-5-phosphonovalerate↗