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 (3ωM) was prevented by pimozide (1mg/kg) but not by pretreatment with L-sulpiride. Addition of L-sulpiride (5ωM) to the Krebs solution had no effect on the inhibition of ACh-evoked release induced by lisuride, but a lower concentration (1ωM) 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.
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