From the Department of Pharmacology, University of Turku, SF-20520 Turku, and Department of Pharmdcology dnd Toxicology, IJnivenity of Kuopio, Finldnd zyxw Presynaptic Dopamine Receptors in the Pithed Rat: Characterization with Apomorphine and Comparison with Central Dopamine Autoreceptors BY J. Hietala, E. MaeDonald and M. Scheinin (Received April 7, 1986, Accepted July 7, 1986) zyxw Abstracl: Apomorphinc, a dopamine agonist with high affinity for presynaptic dopamine receptors, caused dose-dependent inhibition (10-300 pg/kg intravenously) of thc 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 a-I-adrenoceptor rnediatcd pressor response to phenylephrine zyxwv (5 pg/kg intravenously) was not significant- ly attenuated by apomorphine. The sensitivity of periphcral presynaptic dopamine receptors was then studied in the cardiovascular system of rats treated subchronically with haloperidol (2 mg/kg, twice daily intraperitoneally for zyxwvutsrq 10 days). The inhibition of sympathetic vasoconstrictor responses exerted by apomorph- ine was found to be enhanced after subchronic haloperidol treatment suggesting the development of presynap- tic dopamine receptor supersensitivity in the periphery. In addition, the previously reported supersensitivity of central dopdmine autoreceptors to low doses of apomorphine could be confirmed in behavioural experiments. zy Key-words: Apomorphine - haloperidol - presynaptic dopdmine receptors - pithed rat. It is now well accepted that specific dopamine (DA) receptors exist both presynaptically on per- ipheral noradrenergic nerves and postsynaptically in some vascular beds (Enero & Langer 1975; Goldberg 1972). These two classes of DA recep- tors with different structural requirements for agonists and antagonists have been designated as DA-2 and DA- 1 receptors, respectively (Gold- berg & Kohli 1983). Activation of DA-2 receptors reduces the release of noradrenaline (NA) from nerve endings as well as end organ responses elic- ited by sympathetic nerve stimulation, whereas DA-I receptors subserve smooth muscle relax- ation and vasodilation. The role of peripheral presynaptic DA recep- tors in the modulation of sympathetic activity is not yet established under normal physiological conditions. However, only acute studies have been performed so far and the effects of e.g. chronic blockade on the sensitivity of peripheral presynap- tic DA receptors are not known. Previously long- term treatment with neuroleptics has increased the sensitivity of central DA autoreceptors to agonists in behavioural, biochemical and electrophysiolog- ical experiments (Burt zyxw et a/. 1977; Fleminger et al. 1983; Gianutsos & Moore 1977; Nowycky & Roth 1977; Serra et a/. 1979). Therefore it was of interest to study whether analogical supersensi- tivity of presynaptic DA receptors would develop also in the periphery after subchronic treatment with haloperidol. The inhibition exerted by apo- morphine (APO) on sympathetic vasoconstrictor responses in the pithed rat was used as in index of peripheral presynaptic DA receptor sensitivity.