GENETIC COMPONENTS OF ETHANOL RESPONSES

被引:20
作者
CRABBE, JC
FELLER, DJ
TERDAL, ES
MERRILL, CD
机构
[1] OREGON HLTH SCI UNIV, DEPT MED PSYCHOL, PORTLAND, OR 97201 USA
[2] OREGON HLTH SCI UNIV, DEPT PHARMACOL, PORTLAND, OR 97201 USA
关键词
COLD/HOT mice; Convulsions; Ethanol; Hypothermia; Pharmacogenetics; Proconvulsant treatments; Selectively bred lines; Withdrawal; WSP/WSR mice;
D O I
10.1016/0741-8329(90)90013-3
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
A powerful technique for determining the role of a particular neurotransmitter in mediating a response to ethanol (EtOH) is the analysis of selectively bred lines of animals. Lines selected for sensitivity and resistance to an EtOH effect differ principally in gene frequencies for genes affecting the selected response. Hence, other differences between the lines are likely due to pleiotropic actions of those genes. We discuss behavioral pharmacological experiments in two sets of selected lines. Withdrawal Seizure-Prone (WSP) and -Resistant(WSR) mouse lines were selected for severe and minimal handling-induced convulsions (HIC), respectively, after withdrawal from chronic EtOH inhalation. The HIC is also elevated after acute administration of low doses of convulsant drugs. WSP mice were found to be more sensitive than WSR mice to many such drugs. There was no apparent specificity of such effects to any particular neurotransmitter system. Thus, genetic determination of a behavioral response to EtOH in this case cannot be traced to the influence of a single neurotransmitter system. COLD and HOT mice were selectively bred to show severe and mild hypothermia, respectively, after acute EtOH administration. COLD mice are also more sensitive to a number of other alcohols, barbiturates, and other general central nervous system depressants. When tested for sensitivity to a number of drugs with specific effects on neurotransmitter systems, COLD and HOT mice did not differ in sensitivity to drugs affecting dopaminergic, α-adrenergic, or nicotinic acetylcholinergic systems, COLD mice were more sensitive, however, to opioid and serotonergic drugs. Thus, analysis of these selected lines was successful in identifying particular neurotransmitters which may be important in EtOH-induced hypothermia. © 1990.
引用
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页码:245 / 248
页数:4
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