URIDINE POTENTIATES HALOPERIDOLS DISRUPTION OF CONDITIONED AVOIDANCE RESPONDING

The pyrimidine nucleoside, uridine, has been proposed as a potential s upplement in the treatment of psychosis based on its ability to reduce haloperidol-induced dopamine release. These experiments investigated the effect of uridine (32 mg/kg, i.p.) coadministered with the neurole ptic haloperidol, on rats engaged in one way conditioned avoidance res ponding. Uridine itself had no effect on animals' performance, while h aloperidol (dose range 0.05-0.4 mg/kg, i.p., 90 min before test sessio n) decreased number of avoidances and increased avoidance and escape l atencies in a dose-dependent manner. When coadministered with haloperi dol, uridine significantly potentiated the disruption of avoidance and avoidance latency induced by haloperidol. This potentiation was still evident after chronic (27 days) uridine treatment. Importantly, coadm inistration of uridine did not potentiate haloperidol-induced increase of escape latency. The potentiation of haloperidol-induced disruption of conditioned avoidance responding suggests that uridine coadministr ation might enhance the antipsychotic action of traditional neurolepti cs. This would allow for a reduction in the therapeutic dose of the an tipsychotic, thereby reducing side effect frequency.