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

Abstract

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 D 3 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,5 H-[1]benzopyrano[4,3b]-1,4-oxasin-9-ol). In combination with the partial, DA D 3 receptor-selective agonist PD151328 (2-[4[3-(4-phenyl)-1-piperazinyl)propoxy]phenyl]-benzamidazole), 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.