Chlordiazepoxide loses its anxiolytic action with long-term treatment.

The biochemical and behavioural effects of acute, 5, 15 and 25 days treatment with chlordiazepoxide (CDP, 5 mg/kg) were examined in the rat. After 5 days of drug treatment, 5-hydroxytryptamine (5HT) levels in the midbrain, hypothalamus and cortex were significantly higher than those of the corresponding controls, and the level of 5-hydroxyindoleacetic acid (5HIAA) was significantly lower, indicating reduced turnover. After 15 days of drug treatment, 5HIAA levels were significantly elevated, compared with the controls, possibly indicating that CDP was blocking the transport of 5HIAA from the brain. This effect appears to be independent of the reduced turnover. After 25 days of drug treatment there were no significant differences compared with the controls. There were no marked changes in noradrenaline and dopamine in any of the areas investigated. It appears that the reduction in 5HT turnover is linked to the anxiolytic effects of CDP; the latter were found after 5 days of drug treatment, but not after 15 or 25 days, using the social interaction test of anxiety.