Analysis of 3-morpholinosydnonimine and sodium nitroprusside effects on dopamine release in the striatum of freely moving rats: role of nitric oxide, iron and ascorbic acid

Abstract

The effects of intrastriatal infusion of 3-morpholinosydnonimine (SIN-1) or sodium nitroprusside (SNP) on dopamine (DA), 3-methoxytyramine (3-MT), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), L-dihydroxyphenylalanine (L-DOPA), ascorbic acid and uric acid concentrations in dialysates from the striatum of freely moving rats were evaluated using microdialysis. SIN-1 (1 mM) infusion for 180 min increased microdialysate DA and 3-MT concentrations, while L-DOPA, DOPCA+HVA, ascorbic acid and uric acid levels were unaffected. Co-infusion with ascorbic acid (0.1 mM) inhibited SIN-1-induced increases in DA and 3-MT dialysate concentration. SNP (1 mM) infusion for 180 min increased greatly the dialysate DA concentration to a peak (2950% of baseline) at the end of the infusion, while increases in 3-MT were negligible. In addition, SNP decreased ascorbic acid and L-DOPA but increased uric acid concentration in the dialysate. Co-infusion with deferoxamine (0.2 mM) inhibited the late SNP-induced increase in DA dialysate concentration, but did not affect the decrease in ascorbic acid and increase uric acid dialysate concentrations. SNP (1 mM) infusion for 20 min moderately increased uric acid, DA and 3-MT, but decreased L-DOPA levels in the dialysate. Ascorbic acid concentration increased at the end of SNP infusion. Co-infusion with ascorbic acid (0.1 mM) inhibited the SNP-induced increase in DA and 3-MT, but did not affect the decrease in L-DOPA and increase in uric acid dialysate concentrations. These results suggest that NO released from SIN-1 may account for the increase in the dialysate DA concentration. NO released following decomposition of SNP may account for the early increase in dialysate DA, while late changes in microdialysate composition following SNP may result from an interaction between NO and the ferrocyanide moiety of SNP. Exogenous ascorbic acid inhibits the effect of exogenous NO on DA release probably by scavenging NO, suggesting that endogenous ascorbic acid may modulate the NO control of DA release from 300 striatal dopaminergic terminals.

Figure 1

Effect of intrastriatal infusion of SIN-1 on DA dialysate concentrations, and effect of ascorbic acid co-infusion on SIN-1-induced changes. Dialysates were collected, at 20 min intervals, for 180 min during drug infusion (horizontal black bar) and for 80 min after discontinuation of drug infusion. Values are given as mean±s.e.mean (n=3). ^*P<0.05 compared with baseline values. +P<0.05 compared with SIN-1 group.

Figure 2

Effect of intrastriatal infusion of SIN-1 (1 mM, n=3), SNP (1 mM, n=3) or deferoxamine 0.2 mM co-infusion with SNP 1 mM (n=4), on ascorbic acid (A), L-DOPA (B, D) and uric acid (C) dialysate concentrations. Dialysates were collected, at 20 min intervals, for 180 min during drug infusion (horizontal black bar) and for 80 min after discontinuation of drug infusion. Values are given as mean±s.e.mean (n=3). ^*P<0.05 compared with baseline values.

Figure 3

Effect of intrastriatal infusion of SNP (1 mM, n=3) on DA dialysate concentrations (A), and effect of deferoxamine (0.2 mM, n=4) co-infusion on SNP-induced change (B). Dialysates were collected, at 20 min intervals, for 180 min during drug infusion (horizontal black bar) and for 80 min after discontinuation of drug infusion. Values are given as mean±s.e.mean. ^*P<0.05 compared with baseline values. +P<0.05 compared with SNP group.

Figure 4

Effect of a short-lasting intrastriatal infusion of SNP (short horizonatal black bar) on DA dialysate concentrations, and effect of ascorbic acid 0.1 mM co-infusion (horizontal black bar) on SNP-induced changes. Dialysates were collected, at 20 min intervals: (a) during SNP infusion and for 200 min after SNP discontinuation; (b) during SNP (20 min)+ascorbic acid 140 min co-infusion, and for 60 min after ascorbic acid discontinuation. Values are given as mean±s.e.mean (n=3). ^*P<0.05 compared with baseline values; +P<0.05 compared with SNP group.

Figure 5

Effect of a short-lasting (20 min) intrastriatal infusion of SNP (1 mM, short horizontal black bar) on ascorbic acid (A), L-DOPA (B) and uric acid (C) dialysate concentrations. The effects of ascorbic acid 0.1 mM co-infusion for 140 min (horizontal black bar) on SNP-induced changes in L-DOPA or uric acid dialysate concentrations are shown in (B) and (C), respectively. Dialysates were collected, at 20 min intervals: (a) during SNP infusion and for 200 min after SNP discontinuation; (b) during SNP (20 min)+ ascorbic acid (140 min) co-infusion, and for 60 min after ascorbic acid discontinuation. Values are given as mean±s.e.mean (n=3). ^*P<0.05 compared with baseline values.

Figure 6

Effect of intrastriatal infusion of potassium ferrocyanide on DA dialysate concentration. Dialysates were collected, at 20 min intervals, for 180 min during drug infusion (horizontal black bar) and for 80 min after drug discontinuation. Values are given as mean±s.e.mean (n=3). ^*P<0.05 compared with baseline values.