Neuroleptic interference with the cocaine cue: internal stimulus control of behavior and psychosis

The ability of cocaine to exert internal stimulus control of behavior was investigated by training rats to discriminate 10 mg/kg cocaine from saline in a discrete-trial, two-lever, food-reward procedure. Acquisition of response control by cocaine (1) succeeded in all animals tested, (2) proceeded rapidly, and (3) was associated with a high Commission Error: Omission Error ratio. These findings support the hypothesis that cocaine, a prototype of drugs inducing a psychotic condition in humans, can act as a powerful internal stimulus in rats. The cocaine cue was also responsive to the action of the dopamine-receptor-blocking agents spiperone (ED50: 0.06 mg/kg), haloperidol (0.24 mg/kg), and pimozide (1.90 mg/kg). d, l-Amphetamine (1.25 mg/kg) induced stimulus generalization with cocaine, and this generalization was blocked by dosages of the same neuroleptics comparable to those of cocaine antagonism. The results are discussed in terms of internal stimulus control of behavior and its relevance to the psychophysiology of schizophrenia.