The importance of calcium in the amphetamine-induced stimulation of dopamine synthesis in mouse striata in vivo

The purpose of this study was to determine the importance of calcium in the stimulation of dopamine (DA) synthesis produced by amphetamine in mouse striata in vivo and the relationship between this effect of amphetamine on DA synthesis to amphetamine-induced circling behavior. The synthesis of DA was initially estimated by injecting [³H]tyrosine i.c.v. and determining the amount of [³H]DA accumulating in the striata. Amphetamine stimulated [³H]DA accumulation, the maximum occurring at a dose of 1 mg/kg; at higher doses, the accumulation of DA was diminished. Ethylene glycol-bis(β-aminoethylether)N,N'-tetraacetic acid (EGTA), injected directly into both striata to remove calcium, had no effect on the control accumulation of [³H]DA, but inhibited the stimulation of [³H]DA accumulation produced by 1 mg/kg of amphetamine. EGTA did not significantly alter [³H]DA accumulation when the dose of amphetamine was 4 mg/kg. It is possible that at higher doses of amphetamine, the accumulation of [³H]DA in the striatum is related to the stimulation of [³H]DA release as well as synthesis. Consequently, we studied the effect of EGTA on [³H]dopa formation after the injection of a decarboxylase inhibitor. Amphetamine, at a dose of 4 mg/kg, increased the formation of [³H]dopa from [³H]tyrosine. EGTA, when applied to the striatum, reduced this stimulation of [³H]dopa formation. The inhibition of synthesis stimulation by EGTA appears to be due to the removal of calcium from the striatum, as the addition of calcium to the EGTA solution reversed this inhibitory effect. These results provide in vivo evidence for the hypothesis that the presence of free calcium ions in the striatum is necessary for the stimulation of DA synthesis produced by amphetamine. Because intrastriatal injection of EGTA has been shown to inhibit the behavioral effects of amphetamine, these results support the hypothesis that the behavioral effects of amphetamine are mediated by the release of a pool of DA that is maintained by the stimulation of DA synthesis.