Genetic regulation of dihydropyridine-sensitive calcium channels in brain may determine susceptibility to physical dependence on alcohol

Caroline H. Brennan, John Jr Crabbe, J. M. Littleton

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Experiments utilising rodents in vivo and cultures of adrenal cells in vitro have suggested that genetic regulation of dihydropyridine-sensitive calcium channels may be involved in dependence on alcohol. Selection of mouse lines for either a very severe ethanol-withdrawal syndrome (withdrawal seizure prone) or a very mild syndrome (withdrawal seizure resistant), has produced lines which differ very markedly in these characteristics. In these experiments, mice bred selectively for these symptoms for 26 generations, were compared for the severity of withdrawal from alcohol after inhalation of ethanol (plus injections of pyrazole) for 3 days. A proportion of animals from each line was killed before withdrawal and membranes from whole brain were analysed by radioligand binding for binding sites for [3H] nitrendipine. Mice which were withdrawal seizure prone showed a markedly greater severity of the ethanol withdrawal syndrome, and also showed a significantly greater up-regulation of binding sites for [3H]nitrendipine with no significant difference in binding affinity. The results suggest a relationship between genetic susceptibility to dependence on alcohol and genetic regulation of neuronal calcium channels in brain.

Original languageEnglish (US)
Pages (from-to)429-432
Number of pages4
JournalNeuropharmacology
Volume29
Issue number5
DOIs
StatePublished - 1990

Fingerprint

Calcium Channels
Alcoholism
Nitrendipine
Seizures
Ethanol
Brain
Binding Sites
Genetic Predisposition to Disease
Inhalation
Rodentia
Up-Regulation
Cell Culture Techniques
Alcohols
Injections
Membranes
1,4-dihydropyridine

Keywords

  • calcium channels
  • dihydropyridine
  • ethanol dependence
  • ethanol withdrawal
  • genetic regulation
  • pyrazole

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

Cite this

Genetic regulation of dihydropyridine-sensitive calcium channels in brain may determine susceptibility to physical dependence on alcohol. / Brennan, Caroline H.; Crabbe, John Jr; Littleton, J. M.

In: Neuropharmacology, Vol. 29, No. 5, 1990, p. 429-432.

Research output: Contribution to journalArticle

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