Presynaptic dopamine receptors in the pithed rat: characterization with apomorphine and comparison with central...

Apomorphine, a dopamine agonist with high affinity for presynaptic dopamine receptors, caused dose-dependent inhibition (10-300 micrograms/kg intravenously) of the stimulation-induced increase in diastolic blood pressure in the pithed rat. This effect of apomorphine could be antagonized with (-)-sulpiride or haloperidol but not with yohimbine or atropine, indicating the involvement of inhibitory dopamine receptors. The alpha-1-adrenoceptor mediated pressor response to phenylephrine (5 micrograms/kg intravenously) was not significantly attenuated by apomorphine. The sensitivity of peripheral presynaptic dopamine receptors was then studied in the cardiovascular system of rats treated subchronically with haloperidol (2 mg/kg, twice daily intraperitoneally for 10 days). The inhibition of sympathetic vasoconstrictor responses exerted by apomorphine was found to be enhanced after subchronic haloperidol treatment suggesting the development of presynaptic dopamine receptor supersensitivity in the periphery. In addition, the previously reported supersensitivity of central dopamine autoreceptors to low doses of apomorphine could be confirmed in behavioural experiments.