Variability in behavioral responses to benzodiazepines in the rat.

The effects of chlordiazepoxide (10 mg/kg) were assessed in a holeboard by the reductions in head-dipping, rearing and locomotor activity; the correlations among all these measures were significant. Test-retest correlations were significant for all but the time spent head-dipping. On the basis of their behavioral responses to chlordiazepoxide six "strong" and six "weak" responders were identified and used for an in vitro electrophysiological study. There were no differences between the two groups in the extent to which flurazepam potentiated muscimol, but picrotoxin showed a greater antagonism of muscimol in slices from "strong" responders and flurazepam showed a greater reduction of picrotoxin potency. There was a significant correlation between the in vitro picrotoxin shift and the chlordiazepoxide-induced reduction in locomotor activity. The correlations between behavioral responses to chlordiazepoxide and the plasma benzodiazepine concentrations were low and only one (for locomotor activity) reached significance.