Effect of dopamine receptor antagonist on in vivo dopamine release induced by intrastriatal perfusion with methamphetamine in freely moving rats

In order to investigate a regulatory role of dopamine receptors in drug-induced release in the striatum, we determined dopamine and its metabolites in dialysates simultaneously with behavioral observations following intrastriatal perfusion with methamphetamine using the transstriatal dialysis method in freely moving rats. Intrastriatal perfusion with methamphetamine (5, 50, 500 microM) for 40 min produced a marked increase in dopamine release and a slight reduction in 3,4-dihydroxyphenylacetic acid release. No significant changes in spontaneous motor activity were observed after methamphetamine at concentrations up to 500 microM. Methamphetamine-induced dopamine release was not affected by the selective D1-receptor antagonist SCH 23390 (1 microM), but was markedly enhanced by the selective D2-receptor antagonist sulpiride (1 microM), at a concentration that did not change the basal level. Intrastriatal pretreatment with kainic acid (1 micrograms into bilateral striata) slightly affected the dopamine release induced by methamphetamine. These results suggest that methamphetamine-induced dopamine release is regulated by both pre- and postsynaptic D-2 receptors in the striatum in vivo.