The preferential dopamine autoreceptor antagonist (+)-UH232 antagonizes the positive reinforcing effects of cocaine and d-amphetamine in the ICSS paradigm.
The dopamine autoreceptor and D3 preferring antagonist [cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin] (+)-UH232, exerts weak stimulatory effects when tested in locomotor activity experiments using habituated animals. (+)-UH232 also blocks d-amphetamine-, cocaine-, and apomorphine-induced hyperactivity, but fails to induce catalepsy. Thus, the behavioral effects of (+)-UH232 appear to be dependent upon the baseline activity of the animal. The antagonistic properties of (+)-UH232 were studied in the intracranial self-stimulation (ICSS) technique in the rat. (+)-UH232 and haloperidol produced inhibitory effects over a wide 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, was significantly weaker in antagonizing cocaine- or d-amphetamine-induced stimulation. This difference between (+)-UH232 and haloperidol with respect to stimulant-blocking ability, support the concept that the effects of (+)-UH232 are not representative of either classical DA agonists or DA antagonists.
Kling-Petersen
T
T
Department of Pharmacology, University of Göteborg, Sweden.
Ljung
E
E
Svensson
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004566:Electrodes; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012653:Self Stimulation / Q000187:drug effects*
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C043425:vanoxerine; C045971:UH 232; D003042:Cocaine; D006220:Haloperidol; D003913:Dextroamphetamine