Evaluation of antagonists of the discriminative stimulus and response rate effects of phencyclidine.

The present studies examined whether a variety of drugs representative of diverse pharmacological classes were able to antagonize either the discriminative stimulus or response rate suppressing effects of phencyclidine (PCP). Rats were trained to lever press according to fixed-ratio 32 reinforcement schedules for food pellet delivery and to discriminate PCP from saline vehicle during daily (Monday-Friday) experimental sessions. Drugs combined with PCP to test for antagonism included an alpha-1 (prazosin) and an alpha-2 (yohimbine) adrenergic antagonist, the adenosine receptor agonist, I-phenylisopropyl adenosine, the gamma-aminobutyric acid agonist, imidazole acetic acid, the dopaminergic antagonist, haloperidol, the acylating agent of the PCP receptor, metaphit, and the dopaminergic drugs (+)- and (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine. All test drugs except metaphit were tested in rats trained to discriminate 2.5 mg/kg of PCP from saline. (+)- and (-)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine were additionally tested in rats trained to discriminate 1.0 mg/kg of PCP from saline. Metaphit was only tested in rats which had been trained to discriminate a 1.0-mg/kg PCP dose. None of the test drugs systematically reduced PCP level selection to vehicle levels. Yohimbine and prazosin, however, but not the other test drugs, partially reversed the response rate reducing effects of PCP. Evidence that alpha adrenergic antagonists have some PCP antagonistic effects were confirmed for the response rate effects of PCP, indicating a possible role of adrenergic mediation of these effects.