Change in nerve terminals of rat striatum after repeated treatment with methamphetamine and haloperidol -morphometrical and electron microscopic monoaminergic histochemical study-

In order to examine the changes in dopaminergic(DA) terminals in rat striatum after methamphetamine(MAP) and/or haloperidol(HAL) treatment, the present study was made. Twenty four rats were used and divided into a control-group, a MAP-group, a HAL-group and a HAL+MAP-group. Rats in these groups received daily intraperitoneal injections of either physiological saline(10ml/kg), MAP(4mg/kg), HAL(5mg/kg) or HAL(5mg/kg) plus MAP(4mg/kg), respectively, for 13days. The reverse tolerance phenomenon was confirmed only in the MAP-group. At 8 and 36days following the daily injection session, rats were killed. Histochemical and morphometrical examination was made on the rat striatum. The number of DA terminals per unit area decreased significantly in both the MAP-group and the HAL-group at the 8th and 36th day (p<0.001), while no change was found in the HAL+MAP-group. The number of non-DA terminals per unit area and the mean area of DA terminals did not differ significantly among the four groups. Density of synaptic vesicles in DA terminals increased significantly only in the HAL+MAP-group at the 36th day(p<0.02). At the 8th day, the number of DA synaptic vesicles per unit area decreased only in the HAL-group(p<0.005), as compared to the control group. At the 36th day, however, it decreased significantly in both the MAP-group(p<0.001) and the HAL-group(p<0.02). It was concluded that the repeated administration of a dopamine agonist and antagonist can result in a morphometrical change in the rat striatal DA terminal, and the change may be long-lasting.