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PCP-based mice models of schizophrenia: differential behavioral, neurochemical and cellular effects of acute and subchronic treatments

AutorCastañé, Anna ; Santana, Noemí ; Artigas, Francesc
Palabras claveDopamine
Working memory
Serotonin
Schizophrenia
Reversal learning
Phencyclidine
NMDA
Glutamate
c-fos
Behavior
Fecha de publicación7-may-2015
EditorSpringer
CitaciónPsychopharmacology 232(21): 4085-4097 (2015)
ResumenRationale N-methyl-D-aspartate receptor (NMDA-R) hypofunction has been proposed to account for the pathophysiology of schizophrenia. Thus, NMDA-R blockade has been used to model schizophrenia in experimental animals. Acute and repeated treatments have been successfully tested; however, long-term exposure toNMDA-R antagonists more likely resembles the core symptoms of the illness. Objectives To explore whether schizophrenia-related behaviors are differentially induced by acute and subchronic phencyclidine (PCP) treatment in mice and to examine the neurobiological bases of these differences. Results Subchronic PCP induced a sensitization of acute locomotor effects. Spontaneous alternation in a T-maze and novel object recognition performance were impaired after subchronic but not acute PCP, suggesting a deficit in working memory. On the contrary, reversal learning and immobility in the tail suspension test were unaffected. Subchronic PCP significantly reduced basal dopamine but not serotonin output in medial prefrontal cortex (mPFC) and markedly decreased the expression of tyrosine hydroxylase in the ventral tegmental area. Finally, acute and subchronic PCP treatments evoked a different pattern of c-fos expression. At 1 h post-treatment, acute PCP increased c-fos expression in many cortical regions, striatum, thalamus, hippocampus, and dorsal raphe. However, the increased c-fos expression produced by subchronic PCP was restricted to the retrosplenial cortex, thalamus, hippocampus, and supramammillary nucleus. Four days after the last PCP injection, c-fos expression was still increased in the hippocampus of subchronic PCP-treated mice. Conclusions Acute and subchronic PCP administration differently affects neuronal activity in brain regions relevant to schizophrenia, which could account for their different behavioral effects
Versión del editorhttp://dx.doi.org/10.1007/s00213-015-3946-6
URIhttp://hdl.handle.net/10261/128835
DOI10.1007/s00213-015-3946-6
Identificadoresdoi: 10.1007/s00213-015-3946-6
issn: 0033-3158
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