The present study was designed to test the hypothesis that chronic lithium (Li) treatment could alter the behavioral manifestations of dopamine (DA) denervation supersensitivity. Rats were maintained on a Li diet continuously for 4 weeks before and 4 weeks after bilateral chemical denervation of DA terminal fields in the nucleus accumbens (N.Acc.) and the caudate nucleus (CN). We examined the behavioral responses of these animals to apomorphine (0.1 mg/kg s.c.) treatment 2 and 4 weeks postdenervation. Animals exposed to similar chemical denervation but maintained on a control diet exhibited well-documented "supersensitive" behavioral responses to apomorphine: N.Acc. denervated animals demonstrated increases in ambulatory sniffing, rearing and locomotor activity; CN-denervated animals demonstrated increases in rearing and focused sniffing in one location but no increases in locomotor activity. Compared to these control-fed animals, Li-diet animals receiving either CN- or N.Acc-denervation demonstrated a significantly decreased "supersensitive" behavioral response to apomorphine. N.Acc.-denervated animals receiving Li showed less apomorphine-induced locomotor activity. CN-denervated animals receiving Li showed less focused behavior which became evident as actual increases in locomotor activity after apomorphine. These results suggest that chronic dietary Li modifies postsynaptic mechanisms to suppress elements of the behavioral manifestations of supersensitive mesolimbic and nigrostriatal DA activity.