Abstract
The genetic relationships between different behaviors used to index the aversive effects of ethanol are unknown. To address this issue, ethanol-induced conditioned place aversion (CPA) was tested in a genetically diverse panel of 15 inbred mouse strains. Mice were exposed to an unbiased place conditioning procedure using ethanol doses of 0, 2, or 4 g/kg; all injections were given immediately after 5-min exposure to distinctive tactile cues. There were dose-dependent effects of ethanol on CPA and on the change in pre-injection activity rates between the first and last conditioning trials. Most strains (80%) developed CPA, demonstrating the generalizability of this behavior. Moreover, genotype had significant effects on CPA magnitude and locomotor activity rates. Strain means from this study and previously published studies were then used to examine genetic correlations. These analyses showed significant genetic correlations between CPA and ethanol intake/preference, conditioned taste aversion, and drug withdrawal (but not blood ethanol concentration or conditioned place preference), supporting the idea of commonality in the genes underlying CPA and each of these behaviors. The overall pattern of findings is consistent with previous data suggesting that genetic differences in sensitivity to ethanol’s aversive effects play a role in determining strain differences in ethanol drinking. The broader implication is that individuals who are more sensitive to the aversive effects of ethanol may be protected from developing the excessive drinking behaviors characteristic of alcohol use disorders.
Highlights
Genotype affects a wide array of responses to ethanol in animals, including changes in locomotor activity, body temperature, ataxia, and loss of righting reflex [1,2]
Given the well-established influence of genotype on alcoholism in humans [3], attention in animal models has focused on genetic variation in phenotypes thought to be relevant for understanding the development, maintenance, and relapse of excessive drinking
The latter possibility is well supported by rodent studies that show a negative genetic relationship between ethanol consumption or preference and sensitivity to ethanol-induced conditioned taste aversion (CTA) [13,17,18]
Summary
Genotype affects a wide array of responses to ethanol in animals, including changes in locomotor activity, body temperature, ataxia, and loss of righting reflex [1,2]. Given the well-established influence of genotype on alcoholism in humans [3], attention in animal models has focused on genetic variation in phenotypes thought to be relevant for understanding the development, maintenance, and relapse of excessive drinking These phenotypes have included such things as ethanol self-administration in operant procedures and ethanol drinking (e.g., [4,5,6,7]), ethanol withdrawal severity [8,9,10], as well as ethanol’s rewarding and aversive effects as indexed by conditioned place preference (CPP) and conditioned taste aversion (CTA) procedures [11,12,13,14].
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