Aims: Haloperidol (HAL) is an antipsychotic drug that has high affinities to the dopamine D(2), but low affinities to D(1) receptors in the brain. Of brain regions, caudate putamen (CP) has the highest levels of the D(1) and D(2) receptors. In this study we evaluated the spatial memory of C57BL/6 mice following chronic administration of HAL and measured levels of D(1) and D(2) receptors in specific brain regions, with the hypothesis that the D(1) and D(2) receptors in CP are important players in spatial memory function of the brain.

Main Methods: C57BL/6 mice received daily intraperitoneal injections of saline or HAL at 1.0 or 2.0mg/kg/day for 3 or 6 weeks. 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. D(1) and D(2) receptors in specific brain regions were measured by Western-blot analysis.

Key Findings: HAL treatment for 6 weeks 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 D(1) and D(2) receptors in CP and up-regulated D(2) receptors in the hippocampus, but did not change the receptors in the prefrontal cortex.

Significance: These results suggest that the D(1) and D(2) receptors in CP are among the main targets of HAL and the receptors in CP play an important role in spatial learning and memory.

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http://dx.doi.org/10.1016/j.lfs.2012.07.025DOI Listing

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