Stimulation of nicotinic acetylcholine alpha7 receptors rescue schizophrenia-like cognitive impairments in rats

被引:13
|
作者
Potasiewicz, Agnieszka [1 ]
Nikiforuk, Agnieszka [1 ]
Holuj, Malgorzata [1 ]
Popik, Piotr [1 ,2 ]
机构
[1] Polish Acad Sci, Inst Pharmacol, Dept Behav Neurosci & Drug Dev, Krakow, Poland
[2] Jagiellonian Univ, Coll Med, Fac Hlth Sci, Krakow, Poland
关键词
Schizophrenia; N-methyl-d-aspartate antagonist model; rats; cognition; alpha7 nicotinic acetylcholine receptor; REACTION-TIME-TASK; POSITIVE ALLOSTERIC MODULATOR; PREPULSE INHIBITION; RECOGNITION MEMORY; WORKING-MEMORY; KNOCKOUT MICE; ENHANCING PROPERTIES; SUSTAINED ATTENTION; IMPAIRED ATTENTION; AGONIST GTS-21;
D O I
10.1177/0269881116675509
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Alpha7 nicotinic acetylcholine receptor (alpha 7 nAChR) dysfunction plays an important role in schizophrenia. Positive allosteric modulators of alpha 7 nAChR have emerged as a promising therapeutic approach to manage cognitive deficits that are inadequately treated in schizophrenic patients. The aim of the present study was to evaluate the ability of type I (CCMI) and type II (PNU120596) alpha 7 nAChR positive allosteric modulators to counteract MK-801-induced cognitive and sensorimotor gating deficits. The activity of these compounds was compared with the action of the alpha 7 nAChR agonist A582941. CCMI, PNU120596 and A582941 reversed the sensorimotor gating impairment evoked by MK-801 based on the prepulse inhibition of the startle response. Additionally, no MK-801-evoked working memory deficits were observed with alpha 7 nAChR ligand pretreatment as assessed in a discrete paired-trial delayed alternation task. However, these compounds did not affect the rats' attentional performances in the five-choice serial reaction time test. The alpha 7 nAChR agents demonstrated a beneficial effect on sensorimotor gating and some aspects of cognition tested in a rat model of schizophrenia. Therefore, these results support the use of alpha 7 nAChR positive allosteric modulators as a potential treatment strategy in schizophrenia.
引用
收藏
页码:260 / 271
页数:12
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