D1 dopamine receptors in the mouse prefrontal cortex: Immunocytochemical and cognitive neuropharmacological analyses

被引:63
作者
Lidow, MS
Koh, PO
Arnsten, AFT
机构
[1] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA
[2] Univ Maryland, Dept Oral & Craniofacial Biol Sci, Baltimore, MD 21201 USA
[3] Univ Maryland, Program Neurosci, Baltimore, MD 21201 USA
关键词
working memory; SKF81297; D1A receptor subtype; D1B receptor subtype;
D O I
10.1002/syn.10143
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dopamine D1 receptors have critical neuromodulatory influences on the working memory functions of the prefrontal cortex, a brain region affected in many neuropsychiatric disorders. When D1 receptor agents are administered to rats or monkeys performing working memory tasks, an "inverted U" dose/response function is typically observed, whereby either too little or too much D1 receptor stimulation impairs working memory. There are two subtypes of D1 receptors, the D1A and the D1B (also known as the D1 and D5, respectively), but the relative contributions of these subtypes to prefrontal cortical function are not known, as there are no pharmacological agents that can distinguish between these receptors. Thus, genetically altered mice are needed to address this question. However, it is not known whether the mouse prefrontal cortex contains both D1A and D1B receptor subtypes, nor is it known whether mice will exhibit responses to D1 receptor agonists similar to those seen in rats and monkeys. The current study examined these issues by immunostaining the mouse brain with specific antibodies directed at the D1A and D1B receptor subtypes and by assessing the effects of increasing doses of a D1 receptor agonist, SKF81297, on spatial working memory performance in mice. Results indicate that mice are generally similar to monkeys and rats, expressing both D1A and D1B receptors in the prefrontal cortex and exhibiting an inverted "U" dose/response curve when administered SKF81297.
引用
收藏
页码:101 / 108
页数:8
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