SCH23390 effects on apomorphine-induced responses of nigral dopaminergic neurons

SCH23390 is a dopamine antagonist which has a high affinity for D₁-like dopaminergic receptors. Receptor binding studies demonstrated significant levels of specific SCH23390 binding within nigral tissue. Therefore, electrophysiological experiments were conducted to determine if this antagonist influenced apomorphine-induced suppressions of unit firing recorded from dopaminergic cells of the substantia nigra zona compacta. Results presented in this report indicate that the autoreceptors located on dendrites and cell bodies of dopamine-containing neurons are not directly acted upon by SCH23390. This conclusion is drawn because: 1) doses of SCH23390 known to block behaviors caused by dopamine agonists were ineffective in blocking rate reductions produced by apomorphine and 2) pretreatment with 0.1 mg/kg of SCH23390 did not change the apomorphine dose-response curve for inhibition of dopaminergic neurons. Consistent with this finding, microinjections of SCH23390 into the zona compacta did not alter apomorphine-induced behaviors which are known to be blocked by haloperidol (a D₂-like antagonist) intranigral injections. However, when only the larger apomorphine doses (64 and 128 μg/kg i.v.) are considered, SCH23390 pretreatment did attenuate the maximum response to apomorphine in some nigral cells. Because larger apomorphine concentrations alter striatal acitivity, such results may be reflective of alterations in a subpopulation of nigral neurons which are postsynaptic to neurons containing D₁-like receptors and located elsewhere in the brain (e.g., in striatum). Collectively, these results agree with previous studies which suggest that dopamine receptors located on dopamine-containing neurons of the substantia nigra zona compacta are likely not of the D₁-type.