Considerable evidence indicates that behavioral effects of dopaminergic drugs may be modified by muscarinic receptor antagonists. The present experiments were conducted to study such interaction in squirrel monkeys that discriminate injections of indirect dopamine agonists with psychomotor stimulant effects from vehicle or, in a separate group, that responded under a fixed-ratio schedule of stimulus-shock termination. Using cumulative dosing procedures, the effects of i.m. doses of cocaine (0.03-3.0 mg/kg), selective D1 -like and D2 -like agonists [R-(+)-6-BrAPB; 0.01-0.3 mg/kg and (+)-PHNO; 0.0001-0.003 mg/kg, respectively], and selective D1 -like and D2 -like antagonists [SCH 39166;0.003-0.1 mg/kg, and haloperidol; 0.001-0.1 mg/kg, respectively] were determined alone and after treatment with scopolamine (0.03 or 0.1 mg/kg). Administered alone, all drugs produced dose-related rete deceasing effects on schedule-controlled responding, and receptor agonists produced cocaine-like dose-related increases on the drug-=associated lever in drug discrimination experiments. Consistent with previous findings, scopolamine dramatically attenuated the behavioral effects of haloperidol, and response rates were at baseline values following the highest dose of the D2 -like antagonist (0.1 mg/kg). Scopolamine also accentuated the dose-related rate-disrupting and discriminative-stimulus effects of cocaine and (+)-PHNO, resulting in a leftward displacement of dose-effect functions. In contrast, the effects of the D1 receptor ligands SCH 39166 and R-(+)-6-BrAPB were less consistently modified by scopolamine. In conjunction, these findings support the view that anticholinergic modification of dopaminergically mediated behavioral
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