Interactions of haloperidol with discriminative responding controlled by 10 mg/kg of cocaine in rats

Nine rats were trained to discriminate 10 mg/kg of cocaine HCI from saline in a two‐lever food‐reinforced drug discrimination procedure. Saline and 0.31–10 mg/kg doses of cocaine were tested for generalization after pretreatment with either vehicle or 0.04 and 0.16 mg/kg of haloperidol. The 0.04 and 0.16 mg/kg doses of haloperidol produced a 2.3 and 5.0‐fold shift to the right, respectively, of the cocaine generalization gradient. Extrapolation of the generalization data suggests that about 3 mg/kg of haloperidol is required to antagonize completely the discriminative effects of the 10 mg/kg training dose of cocaine. Cocaine (0.63 mg/kg) reversed the rate‐depressant effects of 0.04 mg/kg of haloperidol, but even 10 mg/kg only partially attenuated the behavioral depression produced by 0.16 mg/kg of haloperidol. Also, up to 10 mg/kg doses of cocaine exerted no reliable effect on the alternative lever responding produced by 0.04 or 0.16 mg/kg of haloperidol. The data suggest that 2.3–5.0‐fold shift of the cocaine gradient, but not a complete blockade of the discriminative effects of the 10 mg/kg training dose of cocaine, can be achieved with doses of haloperidol at which the drug presumably interacts in a specific manner with dopamine receptors in the brain.