Role of training conditions in discrimination of central nervous system stimulants by rats

Amphetamine and some related compounds were compared in rats trained to discriminate (+)-amphetamine (0.4,1.0 or 1.6 mg/kg) or cocaine (10.0 mg/kg) from the nondrug condition in a standard, two-bar procedure with food reinforcement (n=5–6). Amphetamine and cocaine were generalized completely with each other, in most cases at dose levels which did not greatly reduce the overall numbers of responses. The ED₅₀ values for amphetamine and cocaine varied with the drug and dose used for training, and it was concluded that the stimuli produced by the two drugs were similar but may not be identical. There was an excellent correlation between ED₅₀ values derived from indices of barselection and percentage-responding on the drug-appropriate bar. Apomorphine was generalized with amphetamine only in the rats trained with the higher doses of amphetamine, and only when administered in doses which greatly reduced the overall number of responses. Para-hydroxyamphetamine increased responding on the drug-appropriate bar only when administered in high doses to the rats trained with the lowest dose of amphetamine (0.4 mg/kg). The results strengthen the evidence that the particular drug and dose level used for training can significantly affect the outcome of generalization tests, and challenge the notion that the discriminability of drugs is an immutable property that is amenable to absolute measurement.