715447

Benzodiazepine/gamma-aminobutyric acid receptor deficit in the midbrain of the seizure-susceptible gerbil.

Article date: 1985/10/1

PubMed ID: 715447

Journal name: Proceedings of the National Academy of Sciences of the United States of America (ISSN: 0027-8424)

ABSTRACT

The density of benzodiazepine/gamma-aminobutyric acid receptor binding sites was lower in the midbrain of seizure-susceptible gerbils compared to control seizure-resistant gerbils. Binding of [3H]diazepam to high-affinity brain-specific sites in membrane homogenates of gerbil brain showed a 20-30% lower binding in midbrain (but not other regions) in adult seizure-susceptible gerbils than in controls. This binding deficit was localized by tissue slice autoradiography with [3H]flunitrazepam to the substantia nigra and mesencephalic periaqueductal gray regions, while higher binding was observed in the interpeduncular nucleus. These differences were also seen in animals sacrificed immediately after a seizure. A parallel deficit of [3H]bicuculline methochloride binding to low-affinity gamma-aminobutyric acid receptors also was seen in the same midbrain regions. Scatchard plot analysis showed that the benzodiazepine binding deficit in the nigra was due to a lower number of binding sites with not significant difference in affinity. Lower [3H]flunitrazepam binding was likewise seen in younger animals (29% lower at 30 days of age, 38% at 60 days, and 21% at 90 days), indicating that the midbrain receptor deficit is present in the seizure-susceptible gerbil prior to the age of onset of seizures at 50-100 days. Therefore, these changes are not likely to result from seizures but reflect genetically determined biochemical differences that could play a role in the expression of seizure susceptibility. The deficit in midbrain benzodiazepine/gamma-aminobutyric acid receptors in the seizure-susceptible gerbil would be consistent with the hypothesis that a deficit of gamma-aminobutyric acid-mediated inhibition might contribute to some kinds of epilepsy.

Author List: Olsen R W, Wamsley J K, McCabe R T, Lee R J, Lomax P

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Receptors, GABA-A; Muscimol; Flunitrazepam; bicuculline methochloride; Pentobarbital; Diazepam; Bicuculline;

Mesh terms: Animals; Bicuculline/analogs & derivatives; Diazepam/metabolism; Disease Models, Animal/genetics; Flunitrazepam/metabolism; Gerbillinae/metabolism; Mesencephalon/analysis; Muscimol/metabolism; Pentobarbital/pharmacology; Receptors, GABA-A/deficiency; Seizures/genetics;

Citations: - 4523020

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