Characterization of the effect of dopamine D-3 receptor stimulation on locomotion and striatal dopamine levels

By examining the effect of dopamine (DA) D-3 receptor stimulation on locomotor activity and extracellular levels of DA in striatum we show that inhibition of locomotor activity induced by DA Dg receptor-selective agonists is mediated by two interacting mechanisms: (1) directly via the stimulation of DA D-3 receptors that inhibit locomotor activity, and (2) indirectly via a decrease in extracellular levels of DA. Thus, the moderately DA D-3 receptor-selective agonist R-(+)-7-OH-DPAT (R-(+)-7-hydroxy-2-(N,N-di-n-propylamino)tetralin) decreased locomotor activity after administration of 10 nmol/kg and extracellular DA levels in accumbens and striatum after administration of 30 nmol/kg. A decrease in locomotor activity that coincided with a decrease in extracellular DA levels in striatum was observed after administration of 100 nmol/kg of the DA D-3, receptor-selective agonist PD128907 ((+)-trans-3,4,4a, 10b-tetrahydro-4-propyl-2 H,5H-[1]benzopyrano[4,3b]-1,4-oxasin-9-ol). In combination with the partial, DA Dg receptor-selective agonist PD151328 (2-[4[3-(4-phenyl)-1- piperazinyl)propoxy]phenyl]-benzamidazol a reversal of the attenuating effect of PD128907 on locomotor activity was observed, without an effect on extracellular levels of DA. In combination with a low - 10 nmol/kg - dose of haloperidol, a reversal of the inhibitory effect of PD128907 on locomotor activity was observed that coincided with an increase in extracellular levels of DA. In the presence of 0.5 mg/kg amphetamine, PD128907 decreased amphetamine-induced locomotor activity. This effect could be reversed by PD151328.