Excitatory neuronal responses to dopamine in the cerebral cortex: involvement of D2 but not D1 dopamine receptors.

Abstract

The technique of microelectrophoresis was used to evaluate the relative contribution of D1 and D2 dopamine receptors towards the mediation of the excitatory response of single neurones to dopamine in the somatosensory cortex of the rat. The selective D1 dopamine receptor agonist, SKF 38393, failed to excite any of the cells to which it was applied. In contrast, the selective D2 dopamine receptor agonist, LY 171555, excited the majority of cells tested. The apparent potency of LY 171555 was significantly lower than that of dopamine. When the mobilities of SKF 38393 and LY 171555 were assessed by an in vitro method, they were found to be at least as great as those of dopamine and phenylephrine, suggesting that the lack of effect of SKF 38393 and the lower apparent potency of LY 171555 compared to dopamine reflect genuine biological phenomena. The alpha 1-adrenoceptor antagonist, prazosin, discriminated between excitatory responses to the alpha 1-adrenoceptor agonist, phenylephrine, and LY 171555: responses to phenylephrine were more susceptible to antagonism than were those to LY 171555. The dopamine receptor antagonist, haloperidol, produced the reverse discrimination: responses to LY 171555 were more affected than were those to phenylephrine. Neither antagonist reduced the response to the control agonist, acetylcholine. When applied continuously with low ejecting currents, LY 171555 antagonized the excitatory response to dopamine while the response to phenylephrine was relatively preserved. The response to acetylcholine was unaffected. When similarly applied, SKF 38393 had no selective action on the response to dopamine. 6 These results suggest that D2 dopamine receptors are involved in mediating the excitatory neuronal response to dopamine in the cerebral cortex, whereas DI dopamine receptors are unlikely to be involved. LY 171555 appears to act as a partial agonist at D2 dopamine receptors in this test system.