Two Topographically, Functionally and Pharmacologically Distinct Dopamine-Sensitive Sites Within the Cat Brain

Ergometrine and its Biphasic Action at Dopaminergic Receptors in the Nucleus Accumbens of Rats

“…In other words, the present study together with the earlier published data from our insti tute (3,7,12,13) suggest that ergometrine exerts a biphasic action at the DAj receptors within the nucleus accumbens of rats: (1) a short-term activation during a period of about 30 min and (2) a long-term inhibition following this initial activation.…”

“…Until recently, it was generally believed that the highly characteristic, behavioural symptoms elicited by apomorphine (10) are produced by activation of DA receptors (8). In 1975. however, we were able to show that the apomorphine-induced gnawing in rats is due to its potency to interfere simultaneously with the DAe and DAj receptors in a diametrically oppo site way (3,4): under certain conditions, apo morphine both stimulates the DAe receptors and inhibits the DAj receptors. Starting from the principle that (a) activation and inhibition of the DAj receptors in apomorphine-treated rats should attenuate and potentiate the apo morphine-induced effect, and (b) ergometrine only affects the DAj receptors on the condition that low doses (1.0 jug) are used, we have chosen apomorphine as a tool to study the biphasic effect of ergometrine at the DAj recep tors.…”

“…As a shift in the dose of subcutaneously administered apomorphine from 0.9 to 1.5 mg/ kg results in a shift from a predominant licking score to a predominant gnawing score (3). the ability of ergometrine to produce a comparable shift in test 1 indicates that ergometrine poten tiates the apomorphine-induced effect.…”

“…In view of the fact that DPI, i.e. an agonist of the DAj receptors in the snail Helix aspersa (16), cat (6) and rat (3,7), produces identical effects, it becomes reasonable to sug gest that activation of DA; receptors underlies the potency of ergometrine to attenuate the apomorphine-induced effects.…”

“…Al though it is not yet known whether there are two distinct types of receptors or, simply, two different states of one type of receptor (2), it turned out that the long-term hyperactivity produced by ergometrine is due to its ability to inhibit the DA2 or so-called DA; receptors in a direct or indirect way, leaving the DA] or so-called DAe receptors unaffected (3,7). As activation of the DA; receptors by means of (3,4-dihydroxyphenylamino)-2-imidazoline (DPI) results in a suppression of the locomotor activity (13), the question arose whether the ergometrine-induced, short-term hypoactivity, which precedes the long-term hyperactivity, might be due to its ability to activate the DA; receptors.…”