ABSTRACT-Since the nucleus accumbens has been hypothesized to centrally mediate the discriminative effects of psychomotor stimulants, the discriminative effects of methamphetamine (MA) as well as dopa mine (DA) and noradrenaline (NA) were observed by intracerebral administration of these drugs into the nucleus accumbens in rats discriminating subcutaneous MA from saline. These rats were trained and main tained to discriminate between MA at 0.5 mg/kg, s.c. and saline under a fixed ratio 10 schedule for food reinforcement in a 2-lever operant chamber situation. Guide cannulae were implanted bilaterally into the nucleus accumbens. In the substitution tests, the drug was administered into the nucleus accumbens. MA at 10 pg per rat substituted for subcutaneous MA in 4 out of 5 rats but neither DA at 10-40 ug per rat (n=7) nor NA at 10-40 pg per rat (n=4) substituted for subcutaneous MA. On the other hand, the same drugs ad ministered into the nucleus accumbens induced increased spontaneous motor activity as also observed in six other untrained rats. MA, DA or NA alone each at 10 pg per rat increased spontaneous motor activity. The discriminative effects of MA are considered to be mediated in the nucleus accumbens of rats. Although DA or NA alone administered into the nucleus accumbens showed similar increasing motor activity effects as those of MA, the discriminative effects of exogenous DA or NA alone administered into the same brain area were different from those of MA in the present experimental condition.Keywords: Drug discrimination, Nucleus accumbens, Methamphetamine, Dopamine, NoradrenalineStudies on the reinforcing and discriminative effects of drugs in animals provide useful information regarding the abuse liability of drugs. Recent studies have shown the in volvement of the mesolimbic and mesocortical dopamine (DA) system in the reinforcing and discriminative effects of psychomotor stimulants (1 3). For example, rats self administered d-amphetamine directly into the nucleus ac cumbens in the mesolimbic pathway (4) and cocaine into the medial prefrontal cortex in the mesocortical pathway (5). Intravenous self-administration of d-amphetamine (6) and cocaine (7 9) was disrupted by blocking DA neu rons or depleting DA in the nucleus accumbens of rats. In drug discrimination studies, d-amphetamine (10) and cocaine (11) administered into the nucleus accumbens of rats substituted for these drugs administered systemically. On the other hand, neither d-amphetamine administered into other areas such as the striatum (10) nor cocaine ad ministered into the medial prefrontal cortex or the stria tum (11) substituted for these drugs administered systemi cally. Thus, the mediation in the nucleus accumbens of the discriminative effects of psychomotor stimulants is indicated. It was also reported from the studies using the in vivo microdialysis technique that d-amphetamine in creased the synaptic concentration of DA in the nucleus accumbens of rats (12, 13). Furthermore, the DA increase caused by d-amphetamine in this brain ...