Abstract
Dopamine receptor partial agonists have been proposed for the management of cocaine addiction. In the present studies, this medication strategy was evaluated in squirrel monkeys that were chronically exposed to the D1 partial agonist SKF 83959 via osmotic minipumps (0.1 mg/kg/hr). In one group, the effects of the D1 agonists SKF 82958 and SKF 38393 on eye blinking were studied before and during chronic treatment. In a second group, lever‐pressing was maintained under concurrent fixed‐ratio schedules of i.v. self‐administration (one lever) and food delivery (second lever); the reinforcing effects of i.v. cocaine were studied before and during chronic treatment. Results show that, prechronically, the D1 agonists SKF 82958 and SKF 38393 produced dose‐related and efficacy‐related increase in rates of eye blinking. Chronic exposure to SKF 83959 produced tolerance to these effects, reflected in >10‐fold rightward (SKF 82958) or downward (SKF 38393) shifts in the dose‐effect functions for eyeblinking. In contrast, the reinforcing strength and dose‐related intake of i.v. cocaine were unchanged during the chronic regimen. These data indicate that tolerance to D1‐mediated effects on overt behavior is produced by chronic D1 receptor activation by SKF 83959. Tolerance is not necessarily accompanied by attenuation of the reinforcing effects of indirect dopaminergic stimulants like cocaine (supported by NIH DA03774).
Published Version
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