Cerebellar and frontal cortical benzodiazepine receptors in human alcoholics and chronically alcohol-drinking rats

E. R. Korpi, M. Uusi-Oukari, K. Wegelius, M. Casanova, M. Zito, Joel Kleinman

Research output: Contribution to journalArticle

Abstract

Postmortem cerebellar and frontal cortical membrane homogenates from human alcoholics, control subjects without neurological or psychiatric illnesses, and rats that chronically drank alcohol were studied to determine the binding characteristics of an imidazobenzodiazepine, [3H]Ro 15-4513. This ligand binds to classical γ-aminobutyric acidA (GABAA)/benzodiazepine receptors, as well as to a "diazempam-insensitive" site associated with the GABAA receptor complex in the cerebellar granule cell layer. There were no differences in the density of the binding sites between alcoholics and their controls, between alcohol-drinking AA rats that had a choice between 10% alcohol or water for about 10 weeks and their controls, or between Wistar rats that had been given 20% alcohol as their only fluid for 4 months and their controls, which were pair-fed isocalorically with sucrose. The affinity for the cerebellar binding of [3H]Ro 15-4513 was higher in the alcoholics than the controls. No differences were observed in the frontocortical binding. No affinity differences were observed in the rat models. There were no differences between the groups in the characteristics of [3H]Ro 15-4513 binding to human cerebellum in the presence of micromolar diazepam, thus revealing the diazepam-insentitive binding. When this component was subtracted from the total cerebellar binding, to reveal the diazepam sensitive binding, both the KD and Bmax were lower in the alcoholic than the control group. The binding of [3H]muscimol, a GABAA,agonist, tended to be higher in the frontal cortices of alcoholics; a similar trend for greater effects was observed in the alcoholics for the GABA inhibition of [3H]Ro 15-4513 binding. These results suggest that no drastic changes occur through chronic alcohol abuse in the numbers of cerebellar and frontocortical benzodiazepine receptors in humans and rodent models; however, the data indicate that the alcoholics have either acquired or innate differences in classical benzodiazepine recognition sites of the cerebellum and in the coupling of these sites to GABAA sites in the frontal cortex, without any differences in cerebellar granule cell-specific diazepam-insensitive [3H]Ro 15-4513 binding sites.

Original languageEnglish (US)
Pages (from-to)774-786
Number of pages13
JournalBiological Psychiatry
Volume31
Issue number8
DOIs
StatePublished - Apr 15 1992
Externally publishedYes

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GABA-A Receptors
Alcoholics
Alcohol Drinking
Diazepam
Alcohols
Frontal Lobe
Cerebellum
Binding Sites
GABA-A Receptor Agonists
Muscimol
Benzodiazepines
gamma-Aminobutyric Acid
Alcoholism
Psychiatry
Sucrose
Wistar Rats
Rodentia
Ro 15-4513
Ligands
Control Groups

ASJC Scopus subject areas

  • Biological Psychiatry

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Cerebellar and frontal cortical benzodiazepine receptors in human alcoholics and chronically alcohol-drinking rats. / Korpi, E. R.; Uusi-Oukari, M.; Wegelius, K.; Casanova, M.; Zito, M.; Kleinman, Joel.

In: Biological Psychiatry, Vol. 31, No. 8, 15.04.1992, p. 774-786.

Research output: Contribution to journalArticle

Korpi, E. R. ; Uusi-Oukari, M. ; Wegelius, K. ; Casanova, M. ; Zito, M. ; Kleinman, Joel. / Cerebellar and frontal cortical benzodiazepine receptors in human alcoholics and chronically alcohol-drinking rats. In: Biological Psychiatry. 1992 ; Vol. 31, No. 8. pp. 774-786.
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AU - Zito, M.

AU - Kleinman, Joel

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N2 - Postmortem cerebellar and frontal cortical membrane homogenates from human alcoholics, control subjects without neurological or psychiatric illnesses, and rats that chronically drank alcohol were studied to determine the binding characteristics of an imidazobenzodiazepine, [3H]Ro 15-4513. This ligand binds to classical γ-aminobutyric acidA (GABAA)/benzodiazepine receptors, as well as to a "diazempam-insensitive" site associated with the GABAA receptor complex in the cerebellar granule cell layer. There were no differences in the density of the binding sites between alcoholics and their controls, between alcohol-drinking AA rats that had a choice between 10% alcohol or water for about 10 weeks and their controls, or between Wistar rats that had been given 20% alcohol as their only fluid for 4 months and their controls, which were pair-fed isocalorically with sucrose. The affinity for the cerebellar binding of [3H]Ro 15-4513 was higher in the alcoholics than the controls. No differences were observed in the frontocortical binding. No affinity differences were observed in the rat models. There were no differences between the groups in the characteristics of [3H]Ro 15-4513 binding to human cerebellum in the presence of micromolar diazepam, thus revealing the diazepam-insentitive binding. When this component was subtracted from the total cerebellar binding, to reveal the diazepam sensitive binding, both the KD and Bmax were lower in the alcoholic than the control group. The binding of [3H]muscimol, a GABAA,agonist, tended to be higher in the frontal cortices of alcoholics; a similar trend for greater effects was observed in the alcoholics for the GABA inhibition of [3H]Ro 15-4513 binding. These results suggest that no drastic changes occur through chronic alcohol abuse in the numbers of cerebellar and frontocortical benzodiazepine receptors in humans and rodent models; however, the data indicate that the alcoholics have either acquired or innate differences in classical benzodiazepine recognition sites of the cerebellum and in the coupling of these sites to GABAA sites in the frontal cortex, without any differences in cerebellar granule cell-specific diazepam-insensitive [3H]Ro 15-4513 binding sites.

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