Discriminative stimulus properties of a low dl-amphetamine dose

Using a two-lever food-reinforced operant procedure, rats (n = 10) were trained to discriminate 0.16 mg/kg dl-amphetamine from saline. Over the dose range 0.08 to 0.63 mg/kg, cue detection was found to be dose-dependent (ED50: 0.13 mg/kg). However, 5 mg/kg dl-amphetamine was not generalized with the standard treatment. Further generalization experiments indicated that hydroxyamphetamine (ED50: 0.16 mg/kg) produces a discriminative stimulus similar to that of 0.16 mg/kg dl-amphetamine. Apomorphine (0.16 mg/kg), chlordiazepoxide (10 mg/kg), desipramine (10 mg/kg), fentanyl (0.04 mg/kg), haloperidol (0.04 mg/kg) and isopropamide (0.04 mg/kg) were not generalized with dl-amphetamine. Haloperidol (0.04 to 0.16 mg/kg) blocked the perception of 0.16 mg/kg dl-amphetamine in a dose-related way (ED50: 0.092 mg/kg). It is concluded that the discriminative stimulus properties of low dl-amphetamine doses differ qualitatively from those of high doses. The discriminative stimulus produced by 0.16 mg/kg dl-amphetamine presumably originates peripherally, whereas that produced by high doses of the drug reportedly is of central origin.