Neonatal MK-801 treatment differentially alters the effect of adolescent or adult MK-801 challenge on locomotion and PPI in male and female rats

J Psychopharmacol. 2013 Sep;27(9):845-53. doi: 10.1177/0269881113497613. Epub 2013 Jul 17.


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.

Keywords: MK-801; NMDA receptor; PPI; locomotor activity; schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dizocilpine Maleate / pharmacology*
  • Female
  • Locomotion / drug effects*
  • Male
  • Motor Activity / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Schizophrenia / diet therapy
  • Schizophrenia / metabolism


  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate