A low dose of the alpha2 agonist clonidine ameliorates the visual attention and spatial working memory deficits produced by phencyclidine administration to rats
A low dose of the alpha2 agonist clonidine ameliorates the visual attention and spatial working memory deficits produced by phencyclidine administration to rats
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DOI：
10.1007/s00213-004-1772-3
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发表时间：
2004-08-01
影响因子：
3.4
通讯作者：
Anzivino, LA
中科院分区：
文献类型：
--
作者：
Jentsch, JD;Anzivino, LA
理由。拟精神病的N-甲基-D-天冬氨酸/谷氨酸受体拮抗剂，如苯环己哌啶（PCP），已被证明在大鼠中产生一系列与精神分裂症相关的行为、神经化学和解剖学变化，包括工作记忆和视觉注意力的损害。α（2）去甲肾上腺素能受体激动剂可乐定可阻止NMDA拮抗剂的某些行为效应，表明单胺能系统介导了这些缺陷的某些方面。目标.我们试图确定可乐定修改PCP诱导的视觉注意和空间工作记忆缺陷的能力。结果在偏侧反应时间任务中，较低剂量的可乐定（10 μ g/kg）改善了PCP（2.5 mg/kg，IP）产生的选择准确性的损害，而较高剂量的可乐定（50 μ g/kg）减慢了反应时间，并诱导了选择准确性的缺陷。高剂量可乐定能有效地抑制PCP引起的运动冲动。此外，可乐定（10微克/公斤）防止PCP诱导的性能缺陷，在一个延迟的不匹配的样本任务。结论.这些数据表明，可乐定可能会减弱PCP引起的注意力和工作记忆缺陷，这可能部分是通过阻止这种拟精神病药物的一些下游神经化学和解剖学效应。
Rationale. Psychotomimetic N-methyl-D-aspartate/glutamate receptor antagonists, such as phencyclidine (PCP), have been shown to produce a spectrum of behavioral, neurochemical and anatomical changes in rats that are relevant to aspects of schizophrenia, including impairments of working memory and visual attention. The alpha(2) noradrenergic receptor agonist clonidine prevents some of the behavioral effects of NMDA antagonists, suggesting that monoaminergic systems mediate some aspects of these deficits. Objectives. We sought to determine the ability of clonidine to modify the PCP-induced deficits of visual attention and spatial working memory in rats. Results. In a lateralized reaction time task, a lower dose of clonidine (10 mug/kg) ameliorated the impairment of choice accuracy produced by PCP (2.5 mg/kg, IP), while the higher dose of clonidine (50 mug/kg) slowed response times and induced a deficit of choice accuracy on its own. The high dose of clonidine effectively prevented the motor impulsivity produced by PCP. In addition, clonidine (10 mug/kg) prevented PCP-induced performance deficits in a delayed non-match to sample task. Conclusions. These data indicate that clonidine may attenuate deficits of attention and working memory produced by PCP, perhaps in part by preventing some of the downstream neurochemical and anatomical effects of this psychotomimetic drug.