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.
Ahlenius
S
S
Department of Behavioral Pharmacology, Astra Arcus AB, Södertälje, Sweden.
Salmi
P
P
D000704:Analysis of Variance; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D001665:Binding Sites; D001831:Body Temperature / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012110:Reserpine / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology*
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; C493595:Drd3 protein, rat; D006834:Hydrazines; D008024:Ligands; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D004295:Dihydroxyphenylalanine; D012110:Reserpine; C004297:3-hydroxybenzylhydrazine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin