Impaired working memory by repeated neonatal MK-801 treatment is ameliorated by galantamine in adult rats.
Early life blockade of the NMDA receptor by using MK-801, a non-competitive NMDA receptor antagonist, induces behavioral changes that mimic several features of schizophrenia. In the current study, we first examined the effects of neonatal MK-801 treatment in male Sprague-Dawley rats on locomotor activity, prepulse inhibition and spatial working memory in adolescence (postnatal day 35, PND35) and adulthood (PND63). Next, we investigated the effects of an acetylcholinesterase inhibitor, galantamine, on working memory deficits induced by MK-801 treatment. Rats were treated with either saline or MK-801 (0.25mg/kg twice daily) at PND 5-14, and the long-term behavioral effects were investigated. MK-801 treated rats showed moderate working memory impairments in adolescence but a pronounced deficit in adulthood. However, locomotion and prepulse inhibition at two life stages were not affected by this treatment. Systemic administration of galantamine (1mg/kg) 30 min before each training session significantly improved neonatal MK-801-induced working memory deficits in adulthood. In conclusion, these results suggest that the neonatal MK-801 treatment-induced selective working memory deficit is related to a change in brain cholinergic systems.
Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, PR China; Institute of Mental Health, Peking University, Beijing, PR China.
Yun-Ai
YA
Su
Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, PR China; Institute of Mental Health, Peking University, Beijing, PR China; Shanxi Dayi Hospital, Taiyuan, Shanxi Province, PR China.
Run-Hu
RH
Huang
Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, PR China; Institute of Mental Health, Peking University, Beijing, PR China.
Xiao-Dong
XD
Wang
Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, PR China; Institute of Mental Health, Peking University, Beijing, PR China.
Ji-Tao
JT
Li
Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, PR China; Institute of Mental Health, Peking University, Beijing, PR China. Electronic address: si.tian-mei@163.com.
Tian-Mei
TM
Si
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D005260:Female; D005702:Galantamine / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
D002800:Cholinesterase Inhibitors; D005702:Galantamine; D016291:Dizocilpine Maleate
Galantamine; MK-801; Schizophrenia; Working memory