Genetic analysis of anxiety-related behaviors and responses to benzodiazepine-related drugs in AXB and BXA recombinant inbred mouse strains.
Recombinant inbred (RI) strains derived from the C57BL/6J and A/J mouse strains were used for behavioral studies designed to estimate the number and location of chromosomal loci responsible for anxiety-related behaviors and differential sensitivity to agonists and inverse agonists of the gamma-aminobutyric acidA (GABAA)/benzodiazepine receptor complex. The phenotypes of the parental inbred strains and of 28 RI strains were characterized for the number of transitions in the light<-->dark exploratory model, anxiolytic response to diazepam, vertical and ambulatory activities in an open field, and sensitivity to the convulsant properties of methyl-beta-carboline-3-carboxylate (beta-CCM). The strain distribution patterns and estimates of the minimal number of loci obtained for each trait suggest that multiple chromosomal loci contribute to differences in anxiety-related behavioral phenotypes and the behavioral responses to diazepam and beta-CCM between C57BL/6J and A/J mice. The best probabilities of linkage were found between the variables characterizing response to diazepam and loci on chromosomes 1 (Xmv-41) and 10 (D10Mit2) and between the sensitivity to the convulsant actions of beta-CCM and locus D15Mit5 on chromosome 15.
Section on Behavioral Neuropharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
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Mathis
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Neumann
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Gershenfeld
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Paul
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Crawley
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000235:genetics*; D001143:Arousal / Q000187:drug effects / Q000235:genetics*; D002874:Chromosome Mapping; D003975:Diazepam / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*
D014151:Anti-Anxiety Agents; D011963:Receptors, GABA-A; D003975:Diazepam