Characterization of clozapine-induced changes in synaptic plasticity in the hippocampal-mPFC pathway of anesthetized rats

Brain Research
M MatsumotoMitsuhiro Yoshioka

Abstract

Synaptic plasticity expressed as long-term potentiation (LTP) in the hippocampal-medial prefrontal cortex (mPFC) pathway is considered to be involved in cognitive function and learning and memory processes, but its synaptic mechanism remains unknown. The present study characterized LTP in the mPFC using the atypical antipsychotic clozapine, with a focus on dopaminergic modulation. The magnitude of LTP was facilitated by pretreatment with clozapine (20 mg/kg, i.p.), but not by the typical antipsychotic haloperidol (1 mg/kg, i.p.). Clozapine-induced LTP augmentation was blocked by the dopamine D(1) receptor antagonist SCH-23390 (10 microg/rat, i.c.v.), but not by the D(2) receptor antagonist remoxipride (10 microg/rat, i.c.v.) or the 5-HT(1A) receptor antagonist WAY-100635 (20 microg/rat, i.c.v.). SCH-23390 (10 microg/rat, i.c.v.) by itself did not affect LTP induction. The D(1) receptor agonist SKF-38393 (10 microg/kg, i.c.v.) facilitated LTP, mimicking the clozapine-induced response. Furthermore, in vivo microdialysis showed that transient increases in mPFC dopamine levels induced by tetanic stimulation sustained facilitation following clozapine administration (20 mg/kg, i.p.). These results demonstrate the importance of the D(...Continue Reading

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Citations

Jan 15, 2010·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yu OhmuraMitsuhiro Yoshioka
Feb 22, 2011·Pharmacogenomics·Fayçal MouaffakMarie Odile Krebs
May 14, 2014·Progress in Neuro-psychopharmacology & Biological Psychiatry·Rae PriceTarek K Rajji
Dec 22, 2009·Expert Review of Neurotherapeutics·S Kristian HillJohn A Sweeney
Sep 3, 2013·Biological & Pharmaceutical Bulletin·Hiroki ShikanaiHiroko Togashi

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