Abstract The pyrimidine nucleoside uridine may reduce side effects associated with antipsychotic medication by interacting with dopamine or GABA neurotransmission. Male Sprague-Dawley rats were used to investigate coadministration of uridine with agents that alter food intake (amphetamine, haloperidol, and chlordiazepoxide) and locomotor activity (methamphetamine and l-dopa). Results indicated that chronic uridine [32.0 mg/kg, intraperitoneally (IP)] alone did not alter milk intake or reduction of milk intake induced by amphetamine (dose range 0.5–2.0 mg/kg, IP) or haloperidol (0.125–1.0 mg/kg, IP), nor did it alter the biphasic response induced by chlordiazepoxide (5.0–40.0 mg/kg, IP). However, uridine-treated animals with unilateral striatal lesions exhibited no rotational behavior in the absence of drug challenge, but showed decreased rotation induced by the dopamine agonist, l-dopa (50.0–200.0 mg/kg, IP) compared with controls. In addition, uridine-treated rats exhibited reduced rotation after repeated injections of methamphetamine (4.0 mg/kg, IP) in contrast to increasingly greater rotation observed in control animals. These results are further evidence that chronic uridine may alter drug-induced dopaminergic activity without exerting effects itself.