Dopamine receptors and sensorimotor behavior in MPTP-treated mice.
The contributions of dopamine (DA) receptor subtypes to sensorimotor behavior was studied in MPTP-treated mice. All DA antagonists studied produced akinesia and catalepsy in control and MPTP-treated mice. The rank order of potency was haloperidol greater than SCH 23390 much greater than L-sulpiride. Combined subthreshold doses of SCH 23390 and L-sulpiride induced marked motor impairments. Dose-response curves for each drug were shifted to the left in the MPTP-treated mice, suggesting behavioral supersensitivity. Pretreatment with the selective D1 agonist SKF 38393 or the selective D2 agonist quinpirole either alone or in subthreshold combination also prevented cold swim-induced motor deficits in the MPTP-treated animals. Haloperidol and SCH 23390 also produced somatosensory neglect in both control and MPTP-treated mice, with haloperidol greater than SCH 23390. Again, a shift of the dose-response curves to the left was observed in the MPTP-treated animals. L-Sulpiride, or another D2 antagonist spiperone, had only minimal effects on somatosensory orientation in both control and MPTP-treated mice. Our studies suggest that both D1 and D2 receptors participate in the expression of motor behavior, while D1 receptors appear to be predominantly responsible for somatosensory orientation.
Weihmuller
F B
FB
Department of Psychology, College of Social and Behavioral Science, Ohio State University, Columbus 43210.
Hadjiconstantinou
M
M
Bruno
J P
JP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009949:Orientation / Q000187:drug effects*; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D013469:Sulpiride; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006220:Haloperidol