HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Modification of ethanol effects by bicuculline: genotype-dependent responses and inheritance.

Abstract
Genetic influences on the interaction between ethanol (ETOH) and gamma-aminobutyric acid (GABA) neurotransmitter systems were evaluated with a survey of responses to coadministration of ETOH and a GABA antagonist, bicuculline, in a battery of inbred mouse strains. The selectively bred ETOH-sensitive Long-Sleep (LS) mice, the relatively ETOH-resistant Short-Sleep (SS) mice, and a genetically heterogeneous stock (GHS) were also evaluated. The effect of bicuculline on ETOH-induced sedation, hypothermia, and blood ethanol content upon recovery from sedation was assessed. Inheritance of these responses was also examined using F1 hybrids. The effect of bicuculline on ETOH-produced narcosis varied widely among stocks and included antagonism, potentiation, and no effect. Changes in ETOH-induced narcosis produced by bicuculline were accompanied by changes in blood ethanol concentrations consistent with an hypothesis of altered central nervous system sensitivity to ETOH. Knowledge of a strain's seizure susceptibility to the GABA antagonist or of its sensitivity to the hypnotic effects of ETOH were of no predictive value in estimating the outcome of coadministration studies, suggesting at least partially separate genetic influences on each phenotype. In cross-breeding studies there was commonly dominance toward a profile of bicuculline antagonism of ETOH narcosis but different patterns of dominance were observed for seizure susceptibility, again indicating separate genetic control. The results suggest considerable complexity of GABAergic involvement in genotype-dependent ETOH sensitivity.
AuthorsT J Phillips, B C Dudek
JournalPsychopharmacology (Psychopharmacology (Berl)) Vol. 98 Issue 4 Pg. 549-55 ( 1989) ISSN: 0033-3158 [Print] Germany
PMID2505298 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Ethanol
  • Bicuculline
Topics
  • Animals
  • Bicuculline (pharmacology)
  • Body Temperature (drug effects)
  • Ethanol (antagonists & inhibitors, pharmacology)
  • Genetics, Behavioral
  • Genotype
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred Strains
  • Postural Balance (drug effects)
  • Seizures (chemically induced)
  • Sleep (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: