title: Neonatal MK-801 treatment differentially alters the effect of adolescent or adult MK-801 challenge on locomotion and PPI in male and female rats.
abstract: Schizophrenia is a neurodevelopmental disorder and is typically "triggered" by subsequent insults in life. The N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) induces locomotor hyperactivity and prepulse inhibition (PPI) deficits, which can mimic the schizophrenia phenotype. In this experiment, we assessed whether neonatal exposure to MK-801 (postnatal days 5-14) could induce sensitization to both hyperactivity and PPI deficit caused by later-life acute MK-801 treatment during adolescence or adulthood. Our results showed that the hyperactivity induced by an acute MK-801 challenge was enhanced in male and female rats after neonatal MK-801 treatment. Notably, in the PPI test, adult female rats neonatally exposed to MK-801 exhibited a significantly greater reduction in PPI in response to acute MK-801 administration, whereas male rats receiving neonatal MK-801 treatment expressed attenuated PPI disruption in adulthood. Our data indicate that a combination of neonatal and later-life NMDA receptor blockades could induce sensitization in the locomotor activity of both sexes in adolescence and adulthood. In addition, a sex difference was observed in the effects of this treatment regime on PPI.
authors.affiliation: Key Laboratory of Mental Health, Ministry of Health, Peking University Institute of Mental Health, Peking University, Beijing, People's Republic of China. si.tian-mei@163.com
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhao
authors.forename: Ji-Tao
authors.initials: JT
authors.lastname: Li
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Li
authors.forename: Run-Hu
authors.initials: RH
authors.lastname: Huang
authors.forename: Yun-Ai
authors.initials: YA
authors.lastname: Su
authors.forename: Tian-Mei
authors.initials: TM
authors.lastname: Si
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012559:Schizophrenia / Q000178:diet therapy / Q000378:metabolism
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
keywords: MK-801; NMDA receptor; PPI; locomotor activity; schizophrenia