title: GABAB receptor activation attenuates the stimulant but not mesolimbic dopamine response to ethanol in FAST mice.
abstract: Neural processes influenced by γ-aminobutyric acid B (GABA(B)) receptors appear to contribute to acute ethanol sensitivity, including the difference between lines of mice bred for extreme sensitivity (FAST) or insensitivity (SLOW) to the locomotor stimulant effect of ethanol. One goal of the current study was to determine whether selection of the FAST and SLOW lines resulted in changes in GABA(B) receptor function, since the lines differ in sensitivity to the GABA(B) receptor agonist baclofen and baclofen attenuates the stimulant response to ethanol in FAST mice. A second goal was to determine whether the baclofen-induced reduction in ethanol stimulation in FAST mice is associated with an attenuation of the mesolimbic dopamine response to ethanol. In Experiment 1, the FAST and SLOW lines were found to not differ in GABA(B) receptor function (measured by baclofen-stimulated [(35)S]GTPγS binding) in whole brain or in several regional preparations, except in the striatum in one of the two replicate sets of selected lines. In Experiment 2, baclofen-induced attenuation of the locomotor stimulant response to ethanol in FAST mice was not accompanied by a reduction in dopamine levels in the nucleus accumbens, as measured by microdialysis. These data suggest that, overall, GABA(B) receptor function does not play an integral role in the genetic difference in ethanol sensitivity between the FAST and SLOW lines. Further, although GABA(B) receptors do modulate the locomotor stimulant response to ethanol in FAST mice, this effect does not appear to be due to a reduction in tonic dopamine signaling in the nucleus accumbens.
authors.affiliation: Dept of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Holstein
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eshleman
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics*; D011485:Protein Binding / Q000187:drug effects; D013460:Sulfur Isotopes / Q000493:pharmacokinetics
chemical_list: D002492:Central Nervous System Depressants; D058786:GABA-B Receptor Agonists; D013460:Sulfur Isotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000431:Ethanol; D001418:Baclofen; D004298:Dopamine