Chronic haloperidol-induced spatial memory deficits accompany the upregulation of D1 and D2 receptors in the caudate putamen of C57BL/6 mouse

Abstract

AimsHaloperidol (HAL) is an antipsychotic drug that has high affinities to the dopamine D2, but low affinities to D1 receptors in the brain. Of brain regions, caudate putamen (CP) has the highest levels of the D1 and D2 receptors. In this study we evaluated the spatial memory of C57BL/6 mice following chronic administration of HAL and measured levels of D1 and D2 receptors in specific brain regions, with the hypothesis that the D1 and D2 receptors in CP are important players in spatial memory function of the brain. Main methodsC57BL/6 mice received daily intraperitoneal injections of saline or HAL at 1.0 or 2.0mg/kg/day for 3 or 6weeks. Two days after the last injection, spontaneous alternation of mice in a Y-maze was evaluated to measure their exploratory behavior and spatial working memory. The Morris water maze test was performed to measure their spatial learning and memory. D1 and D2 receptors in specific brain regions were measured by Western-blot analysis. Key findingsHAL treatment for 6weeks decreased the spontaneous alternation of mice in Y-maze, altered the acquisition process and impaired spatial memory in Morris water maze. The same treatment increased levels of D1 and D2 receptors in CP and up-regulated D2 receptors in the hippocampus, but did not change the receptors in the prefrontal cortex. SignificanceThese results suggest that the D1 and D2 receptors in CP are among the main targets of HAL and the receptors in CP play an important role in spatial learning and memory.