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- Title
Dopamine and Benzodiazepine-Dependent Mechanisms Regulate the EtOH-Enhanced Locomotor Stimulation in the GABA<sub>A</sub> α1 Subunit Null Mutant Mice.
- Authors
June Sr., Harry L.; Foster, Katrina L.; Eiler II, William J. A.; Goergen, Joshua; Cook, Jason B.; Johnson, Nathan; Mensah-Zoe, Boikai; Simmons, Jothan O.; Wenyuan Yin; Cook, James M.; Homanics, Gregg E.; June Jr., Harry L.
- Abstract
The present study investigated the role of the α1-containing GABAA receptors in the neurobehavioral actions of alcohol. In Experiment 1, mice lacking the α1 subunit (α1 (−/−)) 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 α1 (−/−) mice were injected with a range of alcohol doses (0.875–4.0 g/kg; i.p.) to evaluate the significance of the α1 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, βCCt) receptor antagonists to attenuate the alcohol-induced stimulant actions. Compared with wild-type mice (α1 (+/+)), 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). βCCt, 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 α1 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 α1 subunit of the GABAA receptor appears to unmask alcohol's stimulatory effects; these effects appear to be regulated via an interaction of both DA- and GABAA BDZ-dependent mechanisms.Neuropsychopharmacology (2007) 32, 137–152. doi:10.1038/sj.npp.1301097; published online 17 May 2006
- Subjects
GABA; AMINO acid neurotransmitters; DOPAMINE; NEUROTRANSMITTERS; ALCOHOL; LABORATORY mice; BENZODIAZEPINES
- Publication
Neuropsychopharmacology, 2007, Vol 32, Issue 1, p137
- ISSN
0893-133X
- Publication type
Article
- DOI
10.1038/sj.npp.1301097