REPEATED QUINPIROLE TREATMENT - LOCOMOTOR-ACTIVITY, DOPAMINE SYNTHESIS, AND EFFECTS OF SELECTIVE DOPAMINE ANTAGONISTS

Repeated treatment with the non-selective dopamine agonist apomorphine results in behavioral sensitization and enhanced dopamine synthesis i n dopamine projection fields. To examine the role of D-2-type dopamine receptors in modulating these effects, the present experiment assesse d the effects of repeated treatment with the D-2-type agonist quinpiro le on locomotor activity and dopamine synthesis. In the first experime nt, rats were treated with vehicle or one of two doses (0.3 or 3.0 mg/ kg) of quinpirole for 8 days. Daily measures of locomotor activity rev ealed an initial suppression of activity produced by quinpirole which dissipated over the 8 days of treatment. A trend for an increase in ac tivity for 3.0 mg/kg quinpirole compared to vehicle was obtained on da y 8. Twenty-four hours after cessation of treatment, dopamine synthesi s, measured as accumulation of 3,4-dihydroxyphenylalanine (DOPA) after treatment with the DOPA decarboxylase inhibitor NSD-1015, was enhance d in the striatum, but not nucleus accumbens-olfactory tubercle (NAOT) or ventral mesencephalon (VM). In Experiment 2, rats were treated for 8 days with vehicle, 3.0 mg/kg quinpirole or the D-1 antagonist SCH 2 3390 (0.5 mg/kg) in a two (vehicle or quinpirole) x two (vehicle or SC H 23390) design. Quinpirole-alone treatment resulted in a reduction of the locomotor suppressant effects of the drug. SCH 23390-alone and qu inpirole-SCH 23390 combined treatment resulted in decreased activity c ompared to the vehicle control group that did not change across days. DOPA accumulation was enhanced in the striatum and NAOT after quinpiro le treatment; however, SCH 23390 had no effect. In Experiment 3, rats were treated for 10 days with vehicle, 3.0 mg/kg quinpirole or the D-2 antagonist eticlopride (1.0 mg/kg) in a two (vehicle or quinpirole) x two (vehicle or eticlopride) design. As in the first two experiments, repeated quinpirole-alone treatment resulted in a reduction of the lo comotor suppressant effects of the drug; however, locomotor activity i n this group was enhanced compared to vehicle controls on day 10. Etic lopride-alone and eticlopride-quinpirole treated rats had suppressed l ocomotor activity across the 10 days. DOPA accumulation was enhanced b y both repeated quinpirole and repeated eticlopride treatment in the s triatum and NAOT. DOPA accumulation in eticlopride-quinpirole treated rats was not different from vehicle control levels in the NAOT, while no significant difference was obtained between the eticlopride-alone a nd eticlopride-quinpirole groups in the striatum. The locomotor activi ty data suggest that repeated quinpirole treatment results in toleranc e to the locomotor suppressant effect of the drug. Evidence for sensit ization was obtained in two out of three of the experiments. These res ults suggest that enhanced dopamine synthesis after repeated non-selec tive dopamine agonist treatment is modulated by D-2-type dopamine rece ptors. (C) 1995 Wiley-Liss, Inc.