Background
Cholinergic neurotransmission notably participates in stress-induced motor responses.
Here we report the contribution of alternative splicing of acetylcholinesterase (AChE)
pre-mRNA to modulate these responses. More specifically, we induced stress-associated
hypofunction of dopaminergic, mainly D2 dopamine receptor–mediated neurotransmission
by haloperidol and explored stress induced hyperlocomotion and catalepsy, an extreme
form of immobility, induced in mice with AChE deficiencies.
Methods
Conditional transgenic (Tet/AS) mice were created with tetracycline-induced antisense
suppression of AChE gene expression. Locomotion and catalepsy times were measured
in Tet/AS and strain-matched control mice, under open-field exposure threat and under
home-cage safety.
Results
In vitro, NGF-treated PC12 cells failed to extend neurites upon Tet/AS suppression.
In vivo, Tet/AS but not control mice showed stress-associated hippocampal deposits
of heat-shock protein 70 and GRP78 (BiP), predicting posttranscriptional changes in
neuronal reactions. Supporting this notion, their striatal cholinergic neurons demonstrated
facilitated capacity for neurite extension, attributing these in vivo changes in neurite
extension to network interactions. Tet/AS mice presented stress-induced hyperlocomotion.
Moreover, the dopamine antagonist haloperidol induced longer catalepsy in threatened
Tet/AS than in control mice. When returned to home-cage safety, Tet/AS mice showed
retarded release from catalepsy.
Conclusions
Acetylcholinesterase modulates stress-induced motor responses and facilitates resumption
of normal motor behavior following stress through both catalytic and noncatalytic
features.
Key Words
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Article info
Publication history
Published online: August 14, 2006
Accepted:
March 23,
2006
Received in revised form:
March 23,
2006
Received:
August 3,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
