Behavioral and biochemical effects of the dopamine D3 receptor-selective ligand, 7-OH-DPAT, in the normal and the reserpine-treated rat.

In normal rats, the dopamine D3 receptor-selective ligand, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT), produced biphasic effects on spontaneous locomotor activity, i.e. suppression at low doses (0.06-0.25 mumol kg-1 s.c.), followed by a gradual increase in motor activity (1.0-4.0 mumol kg-1). The core temperature was decreased at these latter high doses only. The reserpine-induced (8.2 mumol kg-1 s.c.) increase in neostriatal 3,4-dihydroxyphenylalanine (DOPA) accumulation, following treatment with m-hydroxybenzylhydrazine-(NSD-1015) (475 mumol kg-1 i.p.), was dose dependently antagonized by 7-OH-DPAT in the dose range 0.02-4.0 mumol kg-1. The reserpine-induced suppression of spontaneous locomotor activity, however, was antagonized at higher doses only (1.0-4.0 mumol kg-1). Finally, there were no region-selective effects of 7-OH-DPAT on DOPA accumulation in the neostriatum. Thus, it appears that the dopamine D3 receptor-preferring ligand, 7-OH-DPAT, displays the profile of a dopamine D2 receptor agonist, pre- and postsynaptically.