Chronic uridine treatment reduces the level of [³H]spiperone‐labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine‐dependent behaviours

Abstract

The effect was studied of chronic uridine treatment on the recovery of striatal D-2 dopamine (DA) receptors after their irreversible blockade by N-ethoxycarbonyl-2-ethoxy-I,2-dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [3H]spiperone as radioligand. Chronic uridine treatment (15 mg kg-1 day-1, i.p., 14 days) causes a reduction of [3H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [3H]spiperone-labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDQ-induced syndrome is more rapid in the young rats treated with uridine than in the saline-treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D-2 DA receptors.

Uridine decreases morphine-induced behavioral sensitization by decreasing dorsal striatal dopamine release possibly via agonistic effects at GABAA receptors

“…In microdialysis experiments, uridine alone failed to alter extracellular DA, but significantly reduced morphineinduced DA release in the dorsal striatum of morphinesensitized mice, the mean DA% change (100-180 min) was more significantly decreased, demonstrating a neuromodulatory property of this substance in the brain. These findings, at least in part, are consistent with previous studies showing that uridine interacts with the dopaminergic system to mediate locomotor activity (Agnati et al, 1989;Farabegoli et al, 1988;Myers et al, 1993Myers et al, , 1995.…”

“…Emerging evidence suggests that uridine, a neuroactive molecule, is involved in dopaminergic activity and related behaviors distinct from its role in pyrimidine metabolism (Connolly and Duley, 1999). Studies have demonstrated that chronic uridine administration reduced DA release evoked by amphetamine and haloperidol (Agnati et al, 1989;Farabegoli et al, 1988). Evidence also exists that chronic administration of uridine markedly decreases the number of striatal DA binding sites (Farabegoli et al, 1988).…”

“…Studies have demonstrated that chronic uridine administration reduced DA release evoked by amphetamine and haloperidol (Agnati et al, 1989;Farabegoli et al, 1988). Evidence also exists that chronic administration of uridine markedly decreases the number of striatal DA binding sites (Farabegoli et al, 1988). In addition, uridine-treated rats with unilateral striatal lesions show a decreased rotation induced by the DA precursor L-dopa or repeated injections of methamphetamine (Myers et al, 1995).…”

“…It has been shown that uridine is able to alter central dopaminergic activity and dopaminergic-mediated behaviors, as well as to interact with GABA binding sites (Guarneri et al, 1983(Guarneri et al, , 1985Kimura et al, 2001). For example, in rodents, chronic uridine treatment modulates amphetamine-induced hyperactivity and enhances the release of DA in the striatum (Myers et al, 1993), reduces rotation after repeated injections of methamphetamine (Myers et al, 1995), and modulates the rate of recovery of striatal DA receptors after their irreversible blockade (Farabegoli et al, 1988). Collectively, the reduction in the number of DA binding sites, the reduction in DA release, and modulation of haloperidol-induced catalepsy are all indicative of a dopaminergic antagonist property of uridine (Myers et al, 1993).…”

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

“…Chronic Urd administration was also found to increase stereotypy scores and catalepsy induced by an acute haloperidol injection (Agnati et al 1989 ) . Furthermore, chronic Urd treatment reduced expression of dopamine receptors and enhanced their turnover rate in the striatum (Farabegoli et al 1988 ) . These data suggest that Urd coadministration might enhance the antipsychotic actions of traditional neuroleptics.…”