Ethanol-induced conditioned taste aversion in BXD recombinant inbred mice. 1998

F O Risinger, and C L Cunningham
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health Sciences University, 97201-3098, USA.

Genetic differences in sensitivity to ethanol's aversive effects may play an important role in the development of alcohol-seeking behavior and alcoholism. The present study examined the development of ethanol-induced conditioned taste aversion in 20 BXD/Ty recombinant inbred strains of mice and their progenitor inbred strains, C57BL/6J (B6) and DBA/2J (D2). Adult male mice were given 1-hr access to a saccharin-flavored solution every 48 hr for 12 days. After all but the first and last saccharin access periods, they received ethanol injections (0, 2, or 4 g/kg, i.p.). Separate groups of unpaired control mice received 4 g/kg of ethanol 1 hr after water access. Saline control mice were also used for examining preference across a wide range of saccharin concentrations (0.019 to 4.864% w/v). As expected, saccharin consumption during taste conditioning declined over conditioning trials in a dose-dependent manner, indicating development of ethanol-induced conditioned taste aversion. Correlational analyses using strain means from recently published papers indicated no significant genetic correlation between taste conditioning and two phenotypes thought to reflect ethanol reinforcement or reward (ethanol drinking, conditioned place preference). However, there were significant genetic correlations between taste conditioning at the high dose and sensitivity to ethanol-induced hypothermia, rotarod ataxia, and acute withdrawal. Quantitative trait locus (QTL) analyses of strain means indicated that taste aversion was associated (p < 0.01) with genetic markers on nine chromosomes (1, 2, 3, 4, 6, 7, 9, 11, and 17). These QTLs were located near several candidate genes, including genes encoding several different acetylcholine receptor subunits, the delta opioid receptor, and two serotonin receptors (1B and 1D). QTLs for saccharin preference were located on several of the same chromosomes (2, 3, 4, 6, and 11). Two of these saccharin QTLs overlap candidate genes influencing sensitivity to sweet or bitter taste stimuli. In general, these findings support the conclusion that multiple genes influence ethanol-induced conditioned taste aversion. Some of these genes appear to influence taste sensitivity, whereas others appear to mediate sensitivity to aversive pharmacological effects of ethanol.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D009042 Motivation Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli. Incentives,Disincentives,Expectations,Disincentive,Expectation,Incentive,Motivations
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011995 Recombination, Genetic Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses. Genetic Recombination,Recombination,Genetic Recombinations,Recombinations,Recombinations, Genetic
D002874 Chromosome Mapping Any method used for determining the location of and relative distances between genes on a chromosome. Gene Mapping,Linkage Mapping,Genome Mapping,Chromosome Mappings,Gene Mappings,Genome Mappings,Linkage Mappings,Mapping, Chromosome,Mapping, Gene,Mapping, Genome,Mapping, Linkage,Mappings, Chromosome,Mappings, Gene,Mappings, Genome,Mappings, Linkage
D003214 Conditioning, Classical Learning that takes place when a conditioned stimulus is paired with an unconditioned stimulus. Reflex, Conditioned,Classical Conditioning,Classical Conditionings,Conditioned Reflex,Conditionings, Classical
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000428 Alcohol Drinking Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking. Alcohol Consumption,Alcohol Intake,Drinking, Alcohol,Alcohol Drinking Habits,Alcohol Drinking Habit,Alcohol Intakes,Consumption, Alcohol,Drinking Habit, Alcohol,Habit, Alcohol Drinking,Habits, Alcohol Drinking,Intake, Alcohol

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