Original Investigations

Psychopharmacology

, Volume 103, Issue 4, pp 557-566

Response to selection for ethanol-induced locomotor activation: genetic analyses and selection response characterization

  • Tamara J. PhillipsAffiliated withResearch Service, VA Medical Center, and Departments of Medical Psychology and Pharmacology, Oregon Health Sciences University
  • , Sue Burkhart-KaschAffiliated withResearch Service, VA Medical Center, and Departments of Medical Psychology and Pharmacology, Oregon Health Sciences University
  • , Erik S. TerdalAffiliated withResearch Service, VA Medical Center, and Departments of Medical Psychology and Pharmacology, Oregon Health Sciences University
  • , John C. CrabbeAffiliated withResearch Service, VA Medical Center, and Departments of Medical Psychology and Pharmacology, Oregon Health Sciences University

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Abstract

Selectively bred FAST mice are highly susceptible, while SLOW mice are less susceptible, to the locomotor stimulant effects of ethanol. Heritability estimates indicate that approximately 15% of the variance in the FAST lines is of additive genetic origin, while low susceptibility is ostensibly nonheritable. Inbreeding has increased at the rate of 2% per generation, but fertility has been unaffected. Measurement reliability for sensitivity to this ethanol effect was high when measured in both circular (r=0.6) and square (r=0.7) open-fields. In addition, our results indicate that we have selected for differences in sensitivity to ethanol rather than for differences in habituation to the test environment. The difference in response to ethanol between FAST and SLOW mice extended to tests varying in duration, and to a range of ethanol doses. We conclude that the divergence between FAST and SLOW mice generalizes to related test parameters, and speculate that the genetic architecture underlying the locomotor stimulant response may be simpler than previously proposed.

Key words

Selective breeding FAST and SLOW mice Ethanol-stimulated activity Heritability