title: Modifications of inhibitory transmission onto pyramidal neurons by postnatal exposure to MK-801: Effects of enriched environment.
abstract: Early enriched environment (EE) prevents several deficits associated with postnatal MK-801 [N-Methyl-d-Aspartate (NMDA) receptor antagonist] treatment such as cognitive and locomotor deficits. We sought physiological correlates to such changes by looking at inhibitory synaptic inputs onto pyramidal cells in a prefrontal cortex slice preparation. Pharmacologically isolated γ-amino-butyric acidA(GABAA) receptor-mediated currents were measured using whole-cell patch clamp recordings. Wistar rats were raised in standard or EE from birth up to the time of experiments and were injected with saline or MK-801 (1mg/kg) on postnatal days (P) 6-10. We recorded miniature inhibitory post-synaptic currents (mIPSCs) of pyramidal cells in layer II/III of prefrontal cortex and measured their frequency, amplitude and kinetics. In control animals, the amplitude and frequency of mIPSCs increased strikingly during development from P21 to P28. MK-801 accelerated the development of mIPSCs frequency but caused a significant decrease in the amplitude of mIPSCs on P28 suggesting a significant reduction of inhibition onto pyramidal cells. EE per se led to a significant increase in both frequency and amplitude of mIPSCs, but its application to MK-801-treated rats resulted in moderate rescue of GABAergic transmission on P28. We conclude that postnatal MK-801 leads to reduced inhibitory transmission onto pyramidal cells of prefrontal cortex at adolescence which may underlie behavioural and morphological differences detected in vivo in rats. EE presentation from birth rather prevents GABAergic alterations associated with postnatal MK-801 treatment at adolescence.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Shojaei
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Afsaneh Kamali
authors.initials: AK
authors.lastname: Anaraki
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Mirnajafi-Zadeh
authors.affiliation: Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran; Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Victoria 3800, Australia. Electronic address: nafiseh.atapour@monash.edu.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Atapour
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004558:Electric Stimulation; D004777:Environment; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology*; D011247:Pregnancy; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D016291:Dizocilpine Maleate; D001640:Bicuculline
keywords: Development; Enriched environment; Inhibitory synaptic currents; NMDA receptor antagonist; Prefrontal cortex; Schizophrenia