Scopolamine interactions with D1 and D2 antagonists on radial-arm maze performance in rats.
Recent evidence indicates that acetylcholine and dopamine play complementary roles in cognitive as well as motor functions. In our previous study, the dopamine receptor blocker, haloperidol, was found to attenuate the radial-arm maze choice accuracy deficit caused by the muscarinic acetylcholine receptor blocker, scopolamine. Haloperidol has activity in blocking both D1 and D2 dopamine receptor subtypes. The current study was conducted to determine whether this dopamine-acetylcholine interaction specifically involved D1 or D2 dopamine receptors. The D1 antagonist, SCH 23390, and the D2 antagonist, raclopride, were administered with a dose of scopolamine which caused choice accuracy deficits in the radial-arm maze. The scopolamine-induced deficit was reversed by SCH 23390, the D1 antagonist, indicating that D1 blockade alone is sufficient to reverse the amnestic effects of muscarinic blockade. There was no indication in this study that the D2 blocker, raclopride, had a similar effect. However, this does not mean that such an effect may not be present at other doses of raclopride or with other D2 antagonists. The present finding that D1 blockade counteracts scopolamine-induced cognitive dysfunction not only furthers the understanding of dopamine-acetylcholine relationships in cognitive function, it also suggests a promising direction for the development of treatments for cognitive dysfunction due to cholinergic loss.
Levin
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Department of Psychology, University of California, Los Angeles 90024.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D002755:Choice Behavior / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D005260:Female; D009949:Orientation / Q000187:drug effects*; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic / Q000187:drug effects; D012457:Salicylamides / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology*
D014150:Antipsychotic Agents; D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D012457:Salicylamides; D020891:Raclopride; D012601:Scopolamine