Effects of neonatal lesions of the medial prefrontal cortex on adult rat behaviour.
While prefrontal lesions in rodents serve as models for frontal lobe syndromes, neonatal lesions are considered as models for disconnection syndromes, such as schizophrenia. We investigated the effect of neonatal lesions of the rat medial prefrontal cortex (mPFC) together with pubertal dexamethasone-challenge on adult rat behaviour and on apomorphine-induced behavioural changes. Adult lesions were used as controls. Rats with neonatal (postnatal day 7) or adult excitotoxic lesions or sham-lesions of the mPFC were tested 9 weeks after surgery. At postnatal day 49 one group of neonatal operated rats were systemically injected with the glucocorticoid receptor agonist dexamethasone (20 mg/kg), in order to simulate stress-induced glucocorticoid receptor activation. Working memory and perseveration was tested in T-maze tasks (continuous delayed alternation and reversal learning). Additionally, locomotor activity and prepulse inhibition (PPI) of startle was tested with and without apomorphine-treatment. Brain tissue damage was assessed using Nissl-staining and parvalbumine-immunocytochemistry. Pronounced thinning of the prelimbic-infralimbic subregion of the mPFC accompanied by altered cytoarchitecture and reduced number of parvalbumine-immunopositive neurones was found after neonatal lesions while adult lesions resulted in loss of neurones accompanied by gliosis. Neonatal lesions increased perseveration in the T-maze tasks and enhanced PPI, while adult lesions induced a working memory deficit. This differential behavioural outcome presumably reflects neurodevelopmentally induced alterations in neuronal circuits after neonatal lesions versus damage to mPFC alone after adult lesions. Dexamethasone-injection at day 49 did not alter behaviour in these tasks. Motor activity was not affected by neonatal or adult lesions but dexamethasone reduced apomorphine-induced hyperlocomotion.
Schwabe
Kerstin
K
Brain Research Institute, Department of Neuropharmacology, University of Bremen, FB2 P.O. Box 330440, 28334 Bremen, Germany. kschwabe@uni-bremen.de
Enkel
Thomas
T
Klein
Steffen
S
Schütte
Michael
M
Koch
Michael
M
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001927:Brain Diseases / Q000503:physiopathology; D002452:Cell Count / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000293:injuries / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012193:Reversal Learning / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D013997:Time Factors
D018491:Dopamine Agonists; D005938:Glucocorticoids; D010320:Parvalbumins; D003907:Dexamethasone; D001058:Apomorphine