PHARMACOLOGY OF ANXIETY

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A. Behavioral genetics of an anxiety-related behavior were analyzed using recombinant inbred mice of the C57BL/6J x A/J cross. Both male and female mice from the parental lines of these two strains showed widely divergent behaviors on the light-dark transitions model of anxiety, the open field test, b-carboline-induced seizures, and passive avoidance. Thirty recombinant inbred strains,(RIS) were obtained from Jackson Laboratories, Bar Harbor, Maine. Behavioral phenotypes of both male and female RIS showed a distribution representing the C57B1/6J phenotype, the A/J phenotype, and gradations of behavioral responses between the two extremes. Quantitative loci analysis, presently being completed, suggests that more than four genes contribute to the variance. B. Pregnenolone sulfate (PS), a modulator of both the GABA and the NMDA receptors, was tested in the passive avoidance task for learning and memory. Dose-response analysis indicated that PS alone had no effect on acquisition or retention, but that PS attenuated the inhibitory effects of the NMDA antagonist, CPP, on memory.