A comparison of dopamine agonist action to inhibit locomotor activity and to induce stereotyped behaviour in the mouse.

51 purported dopamine agonists from the phenylethylamine, tetralin, octahydrobenzo(f)- and (g)quinoline, benzocycloheptene, aporphine and ergoline series were tested in the mouse for ability to cause motor inhibition at low doses and stereotyped responding (motor facilitation) at higher doses. Motor inhibition was characterised either by a freezing akinesia (spiroperidol sensitive) or by sedation (resistant to spiroperidol). Agents potent to induce the freezing response could, if the dose was raised sufficiently (at least 10 fold), cause stereotypy. Within all series tested N-n-propyl substitution generally conferred greatest selectivity of motor inhibitory action. Radioligand binding assays using [3H]ADTN as ligand and rat striatal tissue showed correlations between abilities to associate with the dopamine receptor and to cause motor inhibition or facilitation, but discrepancies were apparent, particularly within the tetralin series. It is concluded that whilst there exists clear potency differences to inhibit locomotor activity and to induce stereotyped behaviour, it is difficult to demonstrate unequivocally an absolute selectivity of dopamine agonist action for the motor inhibitory dopamine system.