TY - JOUR
T1 - Genetic components of ethanol responses
AU - Crabbe, John C.
AU - Feller, Daniel J.
AU - Terdal, Erik S.
AU - Merrill, Catherine D.
N1 - Funding Information:
arej ustb eginningto be employedfo r pharmacogeneatinca lyses. conductintgh esee xperimentTsh. eses tudiesw eres upportebdy a grant The ability to test pharmacologicahly pothesessu ggestedb y from the Depamnenot f VeteransA ffairs; by PHS-ADAMHA-NIAAA behavioraaln alysessu cha st hosed iscusseadb ovew ill certainlyb e GrantsA A05828,A A06243,A A06498,a ndA A07573~an db y Contract enhancedb y study of the activity of neurotransmitter-specificN umbe2r 71-87-812f0ro mN IDA.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
KW - COLD/HOT mice
KW - Convulsions
KW - Ethanol
KW - Hypothermia
KW - Pharmacogenetics
KW - Proconvulsant treatments
KW - Selectively bred lines
KW - WSP/WSR mice
KW - Withdrawal
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UR - http://www.scopus.com/inward/citedby.url?scp=0025071806&partnerID=8YFLogxK
U2 - 10.1016/0741-8329(90)90013-3
DO - 10.1016/0741-8329(90)90013-3
M3 - Article
C2 - 2184836
AN - SCOPUS:0025071806
SN - 0741-8329
VL - 7
SP - 245
EP - 248
JO - Alcohol
JF - Alcohol
IS - 3
ER -