ANTAGONISM OF COCAINE SELF-ADMINISTRATION BY THE PREFERENTIAL DOPAMINE AUTORECEPTOR ANTAGONIST, (-AJ-76())

(+)-AJ 76 is a presumed preferential dopamine (DA) autoreceptor antago nist which, in previous behavioral investigations, has displayed prope rties characteristic of both DA agonists and DA antagonists. In an att empt to test the hypothesis that (+)-AJ 76 might be an effective cocai ne pharmacotherapy, the present experiments evaluated (+)-AJ 76's beha vioral profile in 3 standard reinforcement paradigms. In the first exp eriment, (+)-AJ 76 paralleled a DA antagonist in that it failed to sup port self-administration behavior at all doses (0.1, 0.32, and 1.0 mg/ kg/inj) tested. In the second experiment, (+)-AJ 76 (0.9, 3.5, and 14. 0 mg/kg) closely resembled the DA agonist D-amphetamine (0.25, 1.0, an d 4.0 mg/kg) in producing a clear dose-dependent conditioned place pre ference. In the third experiment, (+)-AJ 76 (1.88, 3.75, 7.5, 15.0, an d 30.0 mg/kg) significantly reduced breaking points (BPs), increased r ates of responding, and delayed the onset of responding for cocaine. W hile (+)-AJ 76 mimics a typical DA antagonist in its ability to reduce BPs and augment rates of responding for cocaine, recent evidence sugg ests that it more closely resembles a DA agonist in its ability to del ay the onset of responding for cocaine. In summary, the present invest igations have shown that (+)-AJ 76's profile in 3 reinforcement paradi gms is unusual and not exclussively representative of either DA agonis ts or DA antagonists. The potential utility for such an agent in treat ing cocaine abuse is discussed.