ANTAGONISM OF THE DISCRIMINATIVE STIMULUS PROPERTIES OF COCAINE WITH THE COMBINATION OF A DOPAMINE D-1 AND D-2 ANTAGONIST

Antagonism of the discriminative stimulus properties of 10 mg/kg cocai ne was studied in rats by use of the dopamine D-1 antagonist SCH 23390 and the D-2 antagonist haloperidol. Whereas SCH 23390 and haloperidol were by themselves unable to antagonize the cueing properties of coca ine, the combination of both dopamine antagonists resulted in a comple te blockade of the cocaine cue. In the presence of a fixed dose of 0.0 1 and 0.04 mg/kg haloperidol, the ED(50)'s (it is the effective dose i n 50% of the animals) of SCH 23390 for cocaine antagonism were 0.033 a nd 0.012 mg/kg, respectively. Similarly, the ED(50)'s of haloperidol i n combination with 0.01 and 0.04 mg/kg SCH 23390 were 0.021 and 0.024 mg/kg. The combined treatment of haloperidol and SCH 23390 resulted in strong response-rate reductions. At all combination regimens resultin g in a complete blockade of the cocaine cue, response rate was reduced to less than 20% of the control values. These results indicate that t he cueing properties of cocaine are both dopamine D-1- and D-2-mediate d and that a combined antagonism of both receptor subtypes can lead to a complete antagonism of the cueing properties of cocaine which is as sociated with severe attenuation of response rate.