A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat

Journal of Psychopharmacology
Ann Li LimDaniel Thomas Malone

Abstract

This study combined two neurodevelopmental manipulations, neonatal MK-801 treatment and isolation rearing, to produce a 'two-hit' model and determine whether two hits induce a more robust behavioural phenotype of an animal model of aspects of schizophrenia compared with individual manipulations alone. The effect of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK-801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10 and were assigned to group or isolation rearing at weaning (PND 21). From PND 77, they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were subjected to three prepulse inhibition (PPI) tests, a locomotor activity assessment and a novel object recognition task. MK-801-treated rats reared in isolation displayed robust PPI disruptions which were consistently manifested in all three tests. PPI deficits were also detected in saline-treated rats reared in isolation but not in all tests. Only the two-hit rats demonstrated hyperlocomotion and impaired object recognition memory. Clozapine restored PPI anomalies in the two-hit rats. The two-hit model showed greater psychotic-like effects than either neonatal MK-801 or isolation rearing alone. The prelim...Continue Reading

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Citations

Sep 13, 2014·Current Behavioral Neuroscience Reports·Alexandra D ForrestSteven J Siegel
Jan 3, 2016·European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology·David J G WatsonKevin C F Fone
Oct 21, 2015·Progress in Neurobiology·Amber L MarriottR Andrew Tasker
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Mar 20, 2021·Behavioural Brain Research·Wiktor BileckiMarzena Maćkowiak
Jul 30, 2021·Environmental Science and Pollution Research International·Murat Sırrı AkosmanHasan Hüseyin Demirel

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Methods Mentioned

BETA
sedation

Software Mentioned

Viewer II
SPSS
Viewer
PASW Statistics

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