The behavioral and biochemical effects of lithium on dopaminergic agonist-induced supersensitivity.

Dopaminergic behavioral supersensitivity may be induced by chronic treatment with either dopaminergic agonists or antagonists. We demonstrate that the development of agonist-induced supersensitivity is resistant to chronic lithium exposure. Furthermore, chronic lithium alone enhances the stereotypic response to acute dopamine agonist administration and this effect of lithium summates with the behavioral augmentation caused by chronic amphetamine exposure. Although marked dopamine-related behavioral changes occur, chronic treatment with amphetamine, lithium, or both had no effect on levels of DA, DOPAC, HVA, and 3MT in either the striatum or nucleus accumbens. These results suggest that chronic amphetamine treatment with or without lithium does not affect presynaptic dopamine metabolism as assessed by metabolite levels. Furthermore, amphetamine-induced behavioral supersensitivity is not a simple function of changes in dopamine metabolism.