MODIFICATION OF THE BEHAVIORAL-EFFECTS OF THE SELECTIVE DOPAMINE D(2)AGONIST (-4-PROPYL-9-HYDROXYNAPHTHOXAZINE BY DOPAMINE ANTAGONISTS IN MONKEYS())

The present studies were conducted to evaluate the modification of the behavioral effects of the selective D2 agonist (+)-4-propyl-9-hydroxy naphthoxazine [(+)-PHNO] by dopamine receptor blockade. In squirrel mo nkeys responding under a fixed-ratio schedule of stimulus-shock termin ation, the effects of (+)-PHNO were determined alone and in combinatio n with the selective D2 antagonist eticlopride, the selective D1 antag onist hydroxy-N-methyl-5H-benzo(d)naphtho-(2,1-b)azepine (SCH 39166), the nonselective D1/D2 antagonist cis-flupentixol or the atypical neur oleptic clozapine. When administered alone, (+)-PHNO produced dose-dep endent decreases in rates of responding. Pretreatment with eticlopride and cis-flupentixol resulted in dose-dependent right-ward shifts of t he (+)-PHNO dose-effect curve, indicative of surmountable antagonism. Pretreatment with SCH 39166 and clozapine failed to antagonize the eff ects of (+)-PHNO and resulted in a downward shift of the (+)-PHNO dose -effect curve. Other experiments were conducted to determine the durat ion of either catalepsy-associated behavior or repetitive scratching p roduced by (+)-PHNO alone and in combination with selected dopamine re ceptor blockers. Low doses of (+)-PHNO (0.001-0.003 mg/kg) increased t he duration of catalepsy-associated behavior, whereas higher doses (0. 003-0.01 mg/kg) restored the duration of catalepsy-associated behavior to control values and produced increases in the duration of repetitiv e scratching. Pretreatment with eticlopride resulted in a rightward sh ift of the dose-effect curve for repetitive scratching induced by (+)- PHNO, indicative of surmountable antagonism. Pretreatment with SCH 391 66 accentuated the catalepsy-associated behavior induced by low doses of (+)-PHNO and decreased the duration of repetitive scratching after high doses of (+)-PHNO.