In this study, we examined the changes in neuronal histamine (HA) release in the rat striatum after acute and repeated administration of methamphetamine (METH). We studied the regulation of METH-induced HA release by dopamine receptors and the relationship between METH-induced HA release and stereotyped behavior. Acute administration of METH (1 mg/kg) significantly increased HA release 60 min later. Pretreatments with the dopamine D2 antagonists sulpiride and haloperidol blocked the METH-induced increase of HA release, whereas pretreatment with a dopamine D1 antagonist, SCH23390, did not. Moreover, repeated administration of METH (3 mg/kg) greatly enhanced the METH-induced increase of HA release 60, 80, 100, 120 and 180 min after rechallenge of METH (1 mg/kg). Repeated treatment with haloperidol and METH blocked the increase of HA release induced by the rechallenge of METH. The METH-induced increase of HA release was still found after the METH-induced stereotyped behavior decreased in both acute and repeated administrations of METH. These findings suggest that the METH-induced HA release in the striatum is controlled by dopamine D2 receptors and may play an important inhibitory role in the METH-induced stereotyped behavior. Furthermore, a persistent change in the HA neuron system through DA neurotransmission may be partially responsible for the METH-induced behavioral sensitization.