Clozapine increases apolipoprotein D expression in rodent brain: towards a mechanism for neuroleptic pharmacotherapy.

Abstract:

:In contrast to typical neuroleptic drugs, which have high affinities for dopamine D2 receptors, clozapine binds to multiple neurotransmitter receptors. The mechanisms responsible for its superior clinical efficacy over typical neuroleptics remain unknown. Using an automated genomics approach, total gene expression analysis (TOGA), we found an approximately threefold increase in the accumulation of the mRNA encoding apolipoprotein D (apoD) in mouse striatum in response to chronic treatment with clozapine. While in control animals, apoD is expressed predominantly in astrocytes, in situ hybridization and immunohistochemical studies indicated a substantial increase in apoD expression in neurons of the striatum, globus pallidus and thalamus after 2 weeks of clozapine treatment. Clozapine-induced increases in apoD expression were also observed in some white matter regions. These results suggest that apoD is a mediator in the mechanisms of clozapine and thus that deficiencies in aspects of lipid metabolism may be responsible for psychoses.

journal_name

J Neurochem

authors

Thomas EA,Danielson PE,Nelson PA,Pribyl TM,Hilbush BS,Hasel KW,Sutcliffe JG

doi

10.1046/j.1471-4159.2001.00027.x

keywords:

subject

Has Abstract

pub_date

2001-02-01 00:00:00

pages

789-96

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

76

pub_type

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