当前位置： SCI文献检索 > JOURNAL OF NEUROSCIENCE RESEARCH期刊下所有文献 > Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex.

Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex.

Abstract：

:In this study, we tested the hypothesis that chronic administration of phencyclidine (PCP), an N-methyl-D-aspartate (NMDA) receptor antagonist, would cause a long-lasting behavioral sensitization associated with neuronal toxicity. Female Sprague-Dawley rats were administered PCP (20 mg/kg, i.p.) once a day for 5 days, withdrawn for 72 hr, placed in locomotor activity chambers, and challenged with 3.2 mg/kg PCP. Following assessment of locomotor activity, the rats were killed and their brains processed for analysis of apoptosis by either electron microscopy or terminal dUTP nick-end labeling (TUNEL). In study I, PCP challenge produced a much more robust and long-lasting increase in locomotor activity in rats chronically treated with PCP than in those chronically treated with saline. In study II, clozapine pretreatment blunted the degree of sensitization caused by PCP. In study I, a marked increase in TUNEL-positive neurons was found in layer II of the olfactory tubercle and piriform cortex of rats chronically treated with PCP. Many of these neurons had crescent-shaped nuclei consistent with apoptotic condensation and margination of nuclear chromatin under the nuclear membrane. Acute PCP had no effect. Electron microscopy revealed that PCP caused nuclear condensation and neuronal degeneration consistent with apoptosis. Cell counts in layer II of the piriform cortex revealed that chronic PCP treatment resulted in the loss of almost 25% of the cells in this region. However, an increase in glial fibrillary acidic protein (GFAP)-positive cells in the molecular layer suggests that this neurotoxicity also may involve necrosis. In study II, the PCP-induced neuronal degeneration was essentially completely abolished by clozapine pretreatment. This pattern of degeneration was found to coincide with the distribution of the mRNA of the NR1 subunit of the NMDA receptor. The relevance of these data to a PCP model of chronic NMDA receptor hypofunction is discussed.

journal_name

J Neurosci Res

journal_title

Journal of neuroscience research

authors

Johnson KM,Phillips M,Wang C,Kevetter GA

doi

10.1002/(SICI)1097-4547(19980615)52:6<709::AID-JNR

subject

Has Abstract

pub_date

1998-06-15 00:00:00

pages

709-22

issue

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19980615)52:6<709::AID-JNR

journal_volume

pub_type

杂志文章

在线工具

Chronic phencyclidine induces behavioral sensitization and apoptotic cell death in the olfactory and piriform cortex.