Abstract
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, GABAAIPSCs 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.
Footnotes
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Send reprint requests to: Thomas V. Dunwiddie, Department of Pharmacology C236, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262. E-mail:Tom.Dunwiddie{at}UCHSC.edu
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↵1 Current address: Neurophysiologie, POB 101007, Heinrich-Heine-Universitat, D-40001 Dusseldorf, Germany.
- Abbreviations:
- GABA
- γ-aminobutyric acid
- IPSC
- inhibitory postsynaptic current
- ILS
- inbred long sleep mice
- HAS1 and HAS2
- high alcohol sensitivity rat lines
- LAS1 and LAS2
- low alcohol sensitivity rat lines
- ISS
- inbred short sleep mice
- DNQX
- 6,7-dinitroquinoxaline-2,3-dione
- APV
- dl-(−)-2-amino-5-phosphonovaleric acid
- CGP 35348
- 3-aminopropyl-(diethoxymethyl)phosphinic acid
- LS
- long sleep
- PK
- protein kinase
- SS
- short sleep
- Received March 31, 2000.
- Accepted July 10, 2000.
- U.S. Government
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