Neonatal exposure to MK-801, an N-methyl-D-aspartate receptor antagonist, enhances methamphetamine-induced locomotion and disrupts sensorimotor gating in pre- and postpubertal rats.
Administration of non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists (e.g. phencyclidine, MK-801) has been shown to elicit behavioral abnormalities related to symptoms of schizophrenia, such as spontaneous locomotor activity and impaired sensorimotor gating, as represented by deficits of prepulse inhibition (PPI). We sought to determine whether transient blockade of NMDA receptors at the neonatal stage would produce dopamine supersensitivity around puberty, as manifested by these behavioral measures. For this purpose, we examined methamphetamine (MAP; 1.0mg/kg, i.p.)-induced locomotor activity and PPI in pre- (postnatal day; PD 36-38) or post- (PD 64-66) puberty in rats administered MK-801 (0.2mg/kg/day, s.c.) between PD 7 and PD 10. Neonatal MK-801 treatment augmented MAP-induced hyperlocomotion especially in the early adulthood, whereas spontaneous locomotor activity and rearing were not changed. MK-801 administration also disrupted PPI without affecting startle amplitudes around puberty. These findings suggest that transient exposure to MK-801 in the neonatal stage causes exaggerated dopamine transmission and cognitive deficits, particularly in the post-puberty stage.
Uehara
Takashi
T
Department of Neuropsychiatry, University of Toyama Graduate School of Medicine and Pharmaceutical Sciences, Sugitani, Toyama, Japan. uehara@med.u-toyama.ac.jp
Sumiyoshi
Tomiki
T
Seo
Tomonori
T
Matsuoka
Tadasu
T
Itoh
Hiroko
H
Suzuki
Michio
M
Kurachi
Masayoshi
M
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000627:therapeutic use; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D008694:Methamphetamine; D016291:Dizocilpine Maleate