Effects of dopamine antagonists on neuronal histamine release in the striatum of rats subjected to acute and chronic treatments with methamphetamine

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.