Long-term effects of neonatal MK-801 treatment on prepulse inhibition in young adult rats

• Published in: Psychopharmacologia 2009-11, Vol.206 (4), p.623-630
• Main Authors: Uehara, Takashi, Sumiyoshi, Tomiki, Seo, Tomonori, Itoh, Hiroko, Matsuoka, Tadasu, Suzuki, Michio, Kurachi, Masayoshi
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Age Factors; Animal behavior; Animals; Animals, Newborn; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Disease Models, Animal; Dizocilpine Maleate - administration & dosage; Dizocilpine Maleate - toxicity; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - administration & dosage; Excitatory Amino Acid Antagonists - toxicity; Humans; Male; Medical sciences; Motor Activity - drug effects; Neurosciences; Neurotransmitters; Original Investigation; Pharmacology; Pharmacology/Toxicology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Reflex, Startle - drug effects; Rodents; Schizophrenia; Schizophrenia - chemically induced; Schizophrenia - physiopathology; Sensory Gating - drug effects
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1527-2

Rationale Blockade of N -methyl- d -asparate (NMDA) receptors has been shown to produce some of the abnormal behaviors related to symptoms of schizophrenia in rodents and human. Neonatal treatment of rats with non-competitive NMDA antagonists has been shown to induce behavioral abnormality in a later period. Objectives The aim of this study was to determine whether brief disruption of NMDA receptor function during a critical stage of development is sufficient to produce sensorimotor-gating deficits in the late adolescence or early adulthood in the rat. Methods Male pups received the NMDA receptor blocker MK-801 (0.13 or 0.20 mg/kg), or an equal volume of saline on postnatal day (PD) 7 through 10. The animals were tested twice for prepulse inhibition (PPI) and locomotor activity in pre- (PD 35-38) and post- (PD 56-59) puberty. Results Neonatal exposure to both doses MK-801 disrupted PPI in the adolescence and early adulthood. Low-dose MK-801 elicited long-term effects on startle amplitudes, whereas high-dose MK-801 did not. Neither dose of MK-801 showed a significant effect on spontaneous locomotor activity, whereas the high dose attenuated rearing. Conclusions The results of this study suggest neonatal exposure to MK-801 disrupted sensorimotor gating in the adolescence and early adulthood stages. These findings indicate that rats transiently exposed to NMDA blockers in neonatal periods are useful for the study of the pathophysiology and treatment of schizophrenia.