The general locus of d-amphetamine-induced discriminative stimuli

The general locus of d-amphetamine discriminative stimuli was investigated using two separate approaches involving intraventricular drug infusions. In the first approach employed, designated Case I, four groups of rats were trained to perform a 2-lever differential response task in operant chambers programmed to reward a multiple DRL-15, DRL-15 second schedule. Each of the four training groups was distinguished from the others by the particular pair of cue conditions employed as training stimuli. For two groups, intraperitoneal injections f 1.5 (group I) and 0.5 (group II) mg/kg d- amphetamine were paired with saline (1 ml/kg) as the stimulus conditions indicating the operative lever during each training session. Group III received two dosages of amphetamine (1.5 versus 0.5 mg/kg) as its training stimuli, and group IV received the same total amount of saline-amphetamine injections, but the injection was paired only with the some operative lever half of the time. Discrimination training consisted of twenty-eight 30-minute daily training sessions. Drug injections were administered fifteen minutes prior to the initiation of each training session. Discriminative control during acquisition training was assessed by means of 10-minute extinction tests given at the beginning of every fifth training session. Following acquisition training, the S's in groups I and II were surgically equipped with intraventricular cannulae aimed at their right lateral ventricles. After recovery, tests for discriminative control were administered every fifth session of refraining. Both groups responded on the saline lever when tested with i.p. injections of 2.5 mg/kg d-hydroxy-amphetamine. Central administration of 50 pg or more in group II (0.5 mg/kg d-amphetamine versus saline), and 100 pg or more in group I (1.5 mg/kg d- amphetamine versus saline) produced amphetamine lever choice responding during testing. But central infusions of 20, 50 and 75 pg p-OH amphetamine were insufficient to produce amphetamine lever choices suggesting that the central action was due to the drug rather than to its metabolite. The second approach, Case II, employed intraventricular infusions of amphetamine (150 pg) and saline (15 pl) as training stimuli in the some type 2-lever differential response task as that in Case I. The S's used in this approach were first implanted surgically with intraventricular cannulae and then subsequently given discrimination training (ten exposures to each condition). Following acquisition training, generalization testing i.p. injections of d- amphetamine (0.5 and 1.5 mg/kg), p-OH amphetamine (2.0 mg/kg) and saline occurred every third session of retraining. These tests demonstrated that intraventricular administrations of amphetamine and saline wore sufficient to produce discriminative control and that such control was also observed in the animals receiving systemic administration of the test compounds. The results of both approaches demonstrate that intraventricular administrations of d -amphetamine are both sufficient and capable of producing a stimulus state that can acquire discriminative control of lever choice behavior in the rat. However, neither intraventricular nor systemic injections of p- OH amphetamine were capable of producing a stimulus condition similar to that produced by either i.p. or intraventricular administrations of d-amphetamine. These findings indicate that the discriminative properties of d-amphetamine are mediated by the drug's direct actions upon the neurons of the central rather than peripheral nervous system.