Characterization of the dopamine D-3 receptor agonist R(+)-7-hydroxy-N, N-di-n-propyl-2-aminotetralin-induced hypo- and hypermotility in mice

The present study was designed to characterize the dopamine D-3 receptor ag onist R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (R(+)-7-OH-DPAT)-induc ed changes in locomotor activity in mice. Although R(+)-7-OH-DPAT (0.01-10 mg/kg) produced a significant decrease in horizontal and vertical motility within 15 min after the start of behavioural measurements, the dopa:mine D- 1 receptor antagonist R(+)-SCH23390 (0.05 mg/kg) and the dopamine D3 recept or antagonist (+)-UH232 (10 mg/kg) had no antagonistic effects on the R(+)- 7-OH-DPAT (3 mg/kg)-induced hypomotility, while the dopamine D-2 receptor a ntagonist S(-)-sulpride (20 mg/kg) augmented it. Although R(+)-7-OH-DPAT (0 .01-1 mg/kg) had no marked effects on horizontal or vertical motility, high er doses (3 and 10 mg/kg) of the:drug produced a significant increase in ho rizontal or vertical motility from 30 to 90 min after the start of the beha vioural measurements. S(-)-sulpiride (20 mg/kg) and (+)-UH232 (10 mg/kg) al most completely inhibited the R(+)-7-OH-DPAT (3 mg/kg)-induced hypermotilit y, whereas the antagonistic effects of R(+)-SCH23390 (0.05 mg/kg) were part ial. These results suggest that the R(+)-7-OH-DPAT-induced hypermotility is mediated principally via dopamine D-2 and D-3 receptors, whereas it is unl ikely that the hypomotility results from the activation of presynaptic dopa mine D-2 or D-3 receptors. Copyright (C) 1999 John Wiley & Sons, Ltd.