DISCRIMINATIVE STIMULUS PROPERTIES OF COCAINE - NEURO-PHARMACOLOGICAL CHARACTERISTICS AS DERIVED FROM STIMULUS-GENERALIZATION EXPERIMENTS

The experiments reported here were undertaken to examine the neuropharmacological characteristics of drugs inducing stimulus generalization with cocaine as a cue. Experiment 1 indicated that d-amphetamine (ED50: 0.17 mg/kg), 1-amphetamine (0.45 mg/kg), methylamphetamine (0.15 mg/kg), methylphenidate (0.55 mg/kg) and nomifensine (0.32 mg/kg) induce stimulus generalization with cocaine in rats trained to discriminate 10 mg/kg cocaine from saline; this generalization occurred in 100% of the animals, proceeded along steep slopes (s: 1.27 to 1.88 in log-probit plots), and was not associated with behaviorally toxic effects. Amantadine (57.8 mg/kg; s=1.85), apomorphine (0.33 mg/kg; s=1.77), piribedil (8.4 mg/kg; s=10.6) and bromocryptine (>40 mg/kg) also induced stimulus generalization to some extent, but this generalization was partial in some cases, proceeded along a shallow slope with piribedil, and was invariably associated with severe rate depressant effects. Ten mg/kg, but not 1.25 mg/kg hydroxyamphetamine induced generalization in 3 out of 8 rats. Experiment 2 revealed that tranylcrypromine (2.5 mg/kg; s=1.7), fentanyl (0.068 mg/kg; s=1.34), morphine (>10 mg/kg), phencyclidine (0.81 mg/kg; s=1.43), and benztropine (9.2 mg/kg) induce stimulus generalization with cocaine, whereas lidocaine, procaine, chlordiazepoxide, imipramine, desipramine, mescaline, LSD, isopropamide, and atropine do not. Experiment 3 shows that propranolol (1.25 to 40 mg/kg) and isoproterenol (0.63 to 2.5 mg/kg) induce a biphasic generalization with cocaine. Experiment 4 discloses that rats trained to discriminate 10 mg/kg propranolol from saline generalize their training drug along a linear gradient, but generalize cocaine along a biphasic gradient. It is suggested (a) that stimulus generalization with cocaine may be contingent upon increasing the functional availability of endogenous dopamine and, perhaps, of norepinephrine irrespective of the presynaptic mechanism from which such increase may result and (b) that differential stimulus generalization of drugs with cocaine (in terms of dose, subjects, slope, and rate effects) may parallel their differential primary reinforcing properties. © 1979.