Striatal cholinergic function reflects differences in D-2 dopaminergic receptor activation.
The ergot derivatives, bromocriptine, lisuride and quinpirole (Ly-171555), activators of D-2 receptors, increased striatal acetylcholine (ACh) content by about 40% and induced a 30% inhibition of ACh evoked release from striatal slices, similar to the effects of the dopaminergic agonist apomorphine. These actions were a consequence of dopaminergic activation since they were antagonized by pretreatment with the neuroleptic agent, pimozide. In contrast, pretreatment with L-sulpiride (100 mg/kg), a specific antagonist for the D-2 dopaminergic receptor only, prevented the rise of ACh levels induced by apomorphine or quinpirole but did not interfere with the lisuride- or bromocriptine- induced ACh increases. Similarly, inhibition of the ACh evoked release produced by lisuride (3 microM) was prevented by pimozide (1 mg/kg) but not by pretreatment with L-sulpiride. Addition of L-sulpiride (5 microM) to the Krebs solution had no effect on the inhibition of ACh-evoked release induced by lisuride, but a lower concentration (1 microM) antagonized the inhibition induced by quinpirole. Lisuride and bromocriptine responses were both insensitive to sulpiride. These results are discussed in terms of different interaction with the dopaminergic D-2 receptors by the drugs studied.
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D008090:Lisuride / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010868:Pimozide; D019257:Quinpirole; D001971:Bromocriptine; D013469:Sulpiride; D008090:Lisuride; D000109:Acetylcholine