Common Quantitative Trait Loci for Alcohol-Related Behaviors and Central Nervous System Neurotensin Measures: Locomotor Activation1
- Alcohol Research Center and School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado
Abstract
We have analyzed LSXSS recumbinant inbred for ethanol-induced activity using 2.0 g/kg ethanol and a new method we call ethanol activation slope. The ethanol activation slope provides a robust dose-response measure of ethanol activation, independent of both activity after saline and the inhibitory effects of ethanol on locomotor activity. These behavioral data were used in a quantitative trait locus analysis to map chromosomal loci involved in ethanol-induced locomotor activity. We tentatively identified seven loci that mediate the low-dose stimulatory effect of ethanol and six loci involved in locomotion after 2.0 g/kg ethanol. Only one of the loci are in common between the two behaviors. We also compared the behavioral quantitative trait locus to those previously identified that are involved in regulating central nervous system neurotensin levels and neurotensin receptor densities. Six chromosomal regions were identified that regulate at least one central nervous system neurotensin measure and an ethanol-induced locomotor behavior. The identification of loci controlling both central nervous system neurotensin levels or neurotensin receptor densities and ethanol-induced locomotor activity strengthens the proposal that neurotensin regulates, in part, ethanol-induced behaviors and central nervous system sensitivity to ethanol.
Footnotes
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Send reprint requests to: Dr. V. Gene Erwin, School of Pharmacy, UCHSC, Box 238, 4200 East 9th Ave., Denver, CO 80262.
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↵1 This work was supported, in part, by USPHS Grants AA 08454 and AA 07330.
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↵2 Current address: Biobehavioral Health Program, College of Health and Human Development, The Pennsylvania State University, University Park, PA 16802.
- Abbreviations:
- NT
- neurotensin
- NTRs
- high- and low-affinity neurotensin receptors
- NTRH
- high-affinity neurotensin receptor
- NTRL
- low-affinity neurotensin receptor
- NT-ir
- neurotensin-immunoreactivity
- QTLs
- quantitative trait loci
- RI
- recombinant inbred
- cM
- centi-Morgan
- CNS
- central nervous system
- HYP
- hypothalamus
- NA
- nucleus accumbens
- STR
- striatum
- FC
- frontal cortex
- POMC
- proopiomelanocortin
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- Received February 19, 1996.
- Accepted October 31, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
