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

Brain Research
Takashi UeharaM Kurachi

Abstract

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.

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Citations

Apr 1, 2011·British Journal of Pharmacology·C A JonesK C F Fone
Jul 29, 2015·Developmental Neurobiology·Vládia Célia Moreira BorellaDanielle Macêdo
Dec 20, 2014·Neuroscience Letters·Mohammad NasehiMohammad-Reza Zarrindast
Feb 6, 2015·Therapeutic Advances in Psychopharmacology·Hannah SteedsJames M Stone
Dec 21, 2019·Behavioural Pharmacology·Pushparaj GawaiRajesh R Ugale
Feb 23, 2021·Frontiers in Pharmacology·Cássio Morais LossVanessa Costhek Abílio
Dec 1, 2018·Progress in Neuro-psychopharmacology & Biological Psychiatry·Suzy Tamie NiigakiVanessa Costhek Abilio

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