Effects of chronic treatment with uridine on striatal dopamine release and dopamine related behaviours in the absence or the presence of chronic treatment with haloperidol.

Uridine (15mg/kg/day, i.p.), haloperidol (1mg/kg/day, i.p.), uridine (15mg/kg/day, i.p.) plus haloperidol (1mg/kg/day, i.p.) or saline have been chronically administered to Sprague-Dawley male rats. Following 1 week of wash-out, the effects of these treatments on basal striatal dopamine (DA) release as well as on the DA release induced by an acute haloperidol challenge (2mg/kg, i.p.) were studied by means of intracerebral microdialysis. Behavioural tests such as haloperidol-induced catalepsy or apomorphine-induced stereotypics were also performed 4-7 days after drug withdrawal. The chronic treatment with uridine alone or associated with haloperidol markedly reduced DA release induced by an acute haloperidol challenge. The behavioural studies also indicated a change in DA-related behaviours in these conditions. The animals chronically treated with uridine showed significant increases in the stereotypy scores and in the catalepsy induced by an acute haloperidol challenge with respect to saline treated rats. The present results indicate that a chronic uridine treatment is able to potentiate the reduction of the striatal DA transmission induced by acute and chronic haloperidol treatment. This finding suggests the possibility to reduce the neuroleptic dose in the treatment of schizophrenia by combining neuroleptic and uridine treatments, thus making it possible to relieve some of the side effects of neuroleptic therapy.