Effect of lithium administration on rat brain 5-hydroxyindole levels in a possible animal model for mania

The effect of short term administration of lithium on the hyperactivity induced by a mixture of d-amphetamine (DEX) and chlordiazepoxide (CDZP) have been examined in the rat and an attempt made to relate this action to changes in brain concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA). The DEX-CDZP mixture caused a large increase in Y-maze entries (P less than 0.001). Lithium (2 or 4 mEq/kg) attenuated the increase in entries (P less than 0.001) and activity cage locomotion (P less than 0.01) without significantly affecting these parameters in saline-treated rats. However, the increased 5-HT concentration (P less than 0.05) found in the midbrain after the DEX-CDZP mixture was not modified by prior administration of lithium. In control rats lithium had no effect on the level of 5-HT in the cerebellum, cerebral cortex, midbrain or striatum. Levels of 5-hydroxyindoleacetic acid (5-HIAA) in all four brain regions were unaffected by both the DEX-CDZP mixture or pretreatment with lithium. The possible action of the DEX-CDZP mixture on central 5-HT systems and the suitability of the hyperactivity induced by the drug mixture as a model for mania is discussed.