Authors: L Zuckerman N Rimmerman I Weiner
Publish Date: 2003/06/24
Volume: 169, Issue: 3-4, Pages: 298-307
Abstract
Latent inhibition LI refers to retarded conditioning to a stimulus as a consequence of its inconsequential preexposure Amphetamineinduced disruption of LI and its potentiation by antipsychotic drugs APDs in the adult rat are wellestablished models of schizophrenia and antipsychotic drug action respectively It is not clear whether LI can be similarly modulated at prepubertal ageIn view of the notion that schizophrenia is a neurodevelopmental disorder whose overt expression depends on postpubertal brain maturational processes we investigated whether several manipulations known to modulate LI in adult rats including systemic administration of amphetamine and the atypical APD clozapine are capable of producing the same effects in prepubertal 35dayold ratsLike in adults LI was present with 40 preexposures and 2 conditioning trials In contrast to findings in adults LI was resistant to disruption by amphetamine at a dose 1 mg/kg that significantly increased locomotor activity as well as by reducing the number of preexposures to ten increasing the number of conditioning trials to five or changing the context between preexposure and conditioning Clozapine 5 mg/kg and the selective 5HT2A antagonist M100907 03 mg/kg administered in conditioning were without an effect on persistent LI with extended conditioning but were capable of disrupting LI when administered in the preexposure stage as found in adultsThe results point to functionality within brain systems regulating LI acquisition but not those regulating LI expression in periadolescent rats further suggesting that postpubertal maturation of the latter systems may underlie schizophreniamimicking LI disruption reported in adult rats following perinatal manipulations and possibly disrupted LI observed in schizophrenia
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