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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2006-12-14
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pubmed:abstractText |
The present study investigated the role of the alpha1-containing GABA(A) receptors in the neurobehavioral actions of alcohol. In Experiment 1, mice lacking the alpha1 subunit (alpha1 (-/-)) were tested for their capacity to initiate operant-lever press responding for alcohol or sucrose. Alcohol intake in the home cage was also measured. In Experiment 2, the alpha1 (-/-) mice were injected with a range of alcohol doses (0.875-4.0 g/kg; i.p.) to evaluate the significance of the alpha1 subunit in alcohol's stimulant actions. In Experiment 3, we determined if the alcohol-induced stimulant effects were regulated via dopaminergic (DA) or benzodiazepine (BDZ)-dependent mechanisms. To accomplish this, we investigated the capacity of DA (eticlopride, SCH 23390) and BDZ (flumazenil, betaCCt) receptor antagonists to attenuate the alcohol-induced stimulant actions. Compared with wild-type mice (alpha1 (+/+)), the null mutants showed marked reductions in both EtOH and sucrose-maintained responding, and home-cage alcohol drinking. The null mutants also showed significant increases in locomotor behaviors after injections of low-moderate alcohol doses (1.75-3.0 g/kg). betaCCt, flumazenil, eticlopride, and SCH 23390 were able to attenuate the alcohol-induced stimulation in mutant mice, in the absence of intrinsic effects. These data suggest the alpha1 receptor plays an important role in alcohol-motivated behaviors; however, it also appears crucial in regulating the reinforcing properties associated with normal ingestive behaviors. Deleting the alpha1 subunit of the GABA(A) receptor appears to unmask alcohol's stimulatory effects; these effects appear to be regulated via an interaction of both DA- and GABA(A) BDZ-dependent mechanisms.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Benzodiazepines,
http://linkedlifedata.com/resource/pubmed/chemical/Carbolines,
http://linkedlifedata.com/resource/pubmed/chemical/Central Nervous System Depressants,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanol,
http://linkedlifedata.com/resource/pubmed/chemical/Flumazenil,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Modulators,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Salicylamides,
http://linkedlifedata.com/resource/pubmed/chemical/eticlopride,
http://linkedlifedata.com/resource/pubmed/chemical/tert-butyl...
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0893-133X
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pubmed:author |
pubmed-author:CookJames MJM,
pubmed-author:CookJason BJB,
pubmed-author:EilerWilliam J AWJ2nd,
pubmed-author:FosterKatrina LKL,
pubmed-author:GoergenJoshuaJ,
pubmed-author:HomanicsGregg EGE,
pubmed-author:JohnsonNathanN,
pubmed-author:JuneHarry LHLJr,
pubmed-author:JuneHarry LHLSr,
pubmed-author:Mensah-ZoeBoikaiB,
pubmed-author:SimmonsJothan OJO,
pubmed-author:YinWenyuanW
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pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
137-52
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pubmed:dateRevised |
2011-5-18
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pubmed:meshHeading |
pubmed-meshheading:16710315-Animals,
pubmed-meshheading:16710315-Behavior, Animal,
pubmed-meshheading:16710315-Benzazepines,
pubmed-meshheading:16710315-Benzodiazepines,
pubmed-meshheading:16710315-Carbolines,
pubmed-meshheading:16710315-Central Nervous System Depressants,
pubmed-meshheading:16710315-Dopamine,
pubmed-meshheading:16710315-Dopamine Antagonists,
pubmed-meshheading:16710315-Dose-Response Relationship, Drug,
pubmed-meshheading:16710315-Drug Interactions,
pubmed-meshheading:16710315-Ethanol,
pubmed-meshheading:16710315-Flumazenil,
pubmed-meshheading:16710315-GABA Modulators,
pubmed-meshheading:16710315-Humans,
pubmed-meshheading:16710315-Male,
pubmed-meshheading:16710315-Mice,
pubmed-meshheading:16710315-Mice, Inbred C57BL,
pubmed-meshheading:16710315-Mice, Knockout,
pubmed-meshheading:16710315-Motor Activity,
pubmed-meshheading:16710315-Receptors, GABA-A,
pubmed-meshheading:16710315-Reinforcement (Psychology),
pubmed-meshheading:16710315-Salicylamides,
pubmed-meshheading:16710315-Self Administration
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pubmed:year |
2007
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pubmed:articleTitle |
Dopamine and benzodiazepine-dependent mechanisms regulate the EtOH-enhanced locomotor stimulation in the GABAA alpha1 subunit null mutant mice.
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pubmed:affiliation |
Division of Alcohol and Drug Abuse, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA. hjune@psych.umaryland.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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