PRESYNAPTIC ALPHA(2A)-ADRENOCEPTORS INHIBIT THE RELEASE OF ENDOGENOUSDOPAMINE IN RABBIT CAUDATE-NUCLEUS SLICES

alpha(2)-Adrenoceptors modulating the release of dopamine were identif ied and characterized in slices of the head of the rabbit caudate nucl eus. Release of endogenous dopamine was measured by fast cyclic voltam metry as the increase in the extracellular concentration of dopamine e licited by electrical stimulation. The electrochemical signal was iden tified as dopamine by means of the oxidation potential, the voltammogr am and the fact that the signal was not changed by desipramine, which inhibits the high affinity uptake of noradrenaline, but was greatly in creased by nomifensine, which in addition inhibits the high affinity u ptake of dopamine. Stimulation by 6 pulses/100 Hz increased the extrac ellular concentration of dopamine by about 85 nM. The selective alpha( 2)-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) reduced this release with an EC(50) of 173 nM and by maxi mally 75%. The alpha(2)-adrenoceptor agonists clonidine and oxymetazol ine only tended to cause a decrease. Six drugs, including oxymetazolin e, were tested as antagonists against UK 14,304. Their order of antago nist potency (pK(D) values in brackets) was rauwolscine (8.0) > oxymet azoline (7.5) > dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB 4101; 7.3) > phentolamine (7.1) > corynanthine (5.1) approximate to p razosin (< 6). Given alone, the antagonists did not change the release of dopamine elicited by 6 pulses/100 Hz, and the same was true for th e dopamine receptor antagonist sulpiride. When caudate slices were sti mulated by 10 pulses/1 Hz, sulpiride increased the release of dopamine . Desipramine and rauwolscine, in contrast, again caused no change. It is concluded that dopaminergic axons in the rabbit caudate nucleus po ssess release-inhibiting alpha(2)-adrenoceptors. The antagonist affini ties indicate that they belong to the alpha(2A) subtype. In this, they agree with all presynaptic alpha(2)-autoreceptors studied so far in r abbits as well as with the alpha(2)-heteroreceptors modulating the rel ease of serotonin in rabbit brain cortex, suggesting that at least the majority of presynaptic alpha(2)-adrenoceptors in the rabbit are alph a(2A). The agonist sensitivity of the caudate presynaptic alpha(2)-adr enoceptors is low in comparison with cerebrocortical presynaptic alpha (2)-autoreceptors, possibly due to absence of a receptor reserve.