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Vol. 295, Issue 2, 741-746, November 2000
-Aminobutyric AcidA Responses Differs in
Lines of Mice and Rats Genetically Selected for Behavioral Sensitivity
or Insensitivity to Ethanol
Department of Veterans Affairs Medical Center, Denver, Colorado
(W.R.P., T.V.D.); and University of Colorado Health Science Center,
Department of Pharmacology, Denver, Colorado (W.P., W.R.P., T.V.D.)
Previous work has demonstrated that in the hippocampal CA1 region of
Sprague-Dawley rats, there are ethanol-sensitive and ethanol-insensitive populations of GABAergic synapses on pyramidal neurons. The present experiments characterized the ethanol sensitivity of these pathways in lines of rats and mice genetically selected for
sensitivity or insensitivity to the behavioral effects of ethanol. In
ethanol-sensitive inbred long sleep mice, GABAA
IPSCs induced by stimulation of proximal (probably somatic) synapses were enhanced by 80 mM ethanol, whereas the distal (i.e., dendritic) pathway was unaffected. Thus, the relative sensitivity of these pathways (proximal > distal) is the same in both Sprague-Dawley rats and in inbred long sleep mice. However, in the ethanol-insensitive inbred short sleep mice, neither proximal nor distal IPSCs were affected by 80 mM ethanol. The ethanol sensitivity of the proximal pathway was also examined in replicate lines of rats selected for
either high ethanol sensitivity or low ethanol sensitivity. GABAA IPSCs in the high ethanol sensitivity lines were
significantly enhanced by 80 mM ethanol, whereas IPSCs in the low
ethanol sensitivity lines were unaffected. Thus, IPSCs evoked via the
proximal pathway were enhanced by ethanol in all the sensitive mouse
and rat lines, and unaffected in all the insensitive lines. These
experiments demonstrate that GABAA synapses in brain differ
in their sensitivity to enhancement by ethanol, and the sensitivity to
such enhancement is under the control of genes that can be selected for
using classical genetic selective breeding based on a behavioral phenotype.
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