THE PREFERENTIAL DOPAMINE AUTORECEPTOR ANTAGONIST (-UH232 ANTAGONIZESTHE POSITIVE REINFORCING EFFECTS OF COCAINE AND D-AMPHETAMINE IN THE ICSS PARADIGM())

The dopamine autoreceptor and D, preferring antagonist )-5-methoxy-1-m ethyl-2-(di-n-propylamino)tetralin] (+)-UH232, exerts weak stimulatory effects when tested in locomotor activity experiments using habituate d animals. (+)-UH232 also blocks d-amphetamine-, cocaine-, and apomorp hine-induced hyperactivity, but fails to induce catalepsy. Thus, the b ehavioral effects of (+)-UH232 appear to be dependent upon the baselin e activity of the animal. The antagonistic properties of (+)-UH232 wer e studied in the intracranial self-stimulation (ICSS) technique in the rat. (+)-UH232 and haloperidol produced inhibitory effects over a wid e dose range. Cocaine, GBR12909 and d-amphetamine clearly lowered ICSS thresholds, indicating stimulatory effects. (+)-UH232 antagonized the stimulatory effects of cocaine, GBR12909, and d-amphetamine, whereas haloperidol, at a dose producing an inhibition similar to (+)-UH232, w as significantly weaker in antagonizing cocaine- or d-amphetamine-indu ced stimulation. This difference between (+)-UH232 and haloperidol wit h respect to stimulant-blocking ability, support the concept that the effects of (+)-UH232 are not representative of either classical DA ago nists or DA antagonists.