Effects of Methamphetamine, Dopamine and Noradrenaline Administered into the Nucleus Accumbens of Rats Discriminating Subcutaneous Methamphetamine

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 dopamine (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 maintained 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 micrograms per rat substituted for subcutaneous MA in 4 out of 5 rats but neither DA at 10-40 micrograms per rat (n = 7) nor NA at 10-40 micrograms per rat (n = 4) substituted for subcutaneous MA. On the other hand, the same drugs administered 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 micrograms 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.