Further evidence for two directions of D-1:D-2 dopamine receptor interaction revealed concurrently in distinct elements of typical and atypical behaviour: studies with the new enantioselective D-2 agonist LY 163502.

The new, extremely potent and enantioselective D-2 agonist LY 163502 failed to induce compulsive stereotyped behaviour. Very low doses (3-6 micrograms/kg) inhibited spontaneous sniffing and locomotion, while higher doses (12-50 micrograms/kg) induced episodes of non-stereotyped sniffing and chewing; these actions showed complete enantioselectivity. Up to 200-fold higher doses modestly induced only locomotion. Responsivity to LY 163502 was enantioselectively blocked by the selective D-2 antagonist R-piquindone. This responsivity was also enantioselectively blocked by the selective D-1 antagonist R-SK&F 83566 but, additionally, episodes of atypical limb/body jerking behaviour were released; thus, LY 163502 induced such jerking only when tonic D-1 activity was suppressed. These data extend our notion that there may be at least two forms of functional interaction between D-1 and D-2 receptor systems: one cooperative, as in the regulation of typical sniffing, and another oppositional, as in the regulation of atypical jerking.