Sex-specific restoration of MK-801-induced sensorimotor gating deficit by environmental enrichment.
Despite ample evidence of N-methyl-D-aspartate (NMDA) receptor dysfunction in schizophrenia, no study has addressed the effects of enriched environment (EE) on sensorimotor gating deficits induced by postnatal NMDA receptor blockade. We evaluated the effect of EE on sensorimotor gating (measured by prepulse inhibition, PPI), or on sensorimotor gating deficit induced by the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) in both sexes of Wistar rats. Rats were injected with MK-801 (1 mg/kg) on postnatal days (P) 6-10. EE was provided from birth up to the time of experiments on P28-30 or P58-60. PPI data were collected at three prepulse intensities and then averaged to yield global PPI. MK-801 treatment reduced PPI significantly in both sexes. While EE per se had no significant effect on PPI, it restored MK-801-induced PPI deficit only in male rats. An extended period of EE did not influence PPI deficit in female rats. Our results indicate that postnatal exposure to MK-801 may exert long-lasting effects on neuronal circuits underlying sensorimotor gating. Sex-specific modulation of such effects by EE suggests sexually dimorphic mechanisms are involved.
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
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Nozari
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
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Shabani
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
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Farhangi
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.
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Mazhari
Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran; Department of Physiology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: nafiseh.atapour@monash.edu.
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Atapour
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004777:Environment; D005260:Female; D008297:Male; D065808:Prepulse Inhibition / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate
NMDA receptor antagonist; prepulse inhibition; rat; schizophrenia