Abstract
Background:
Changes in neuroplasticity have been involved in the pathogenesis of psychiatric disorders
as well as in psychotropic drug action. Calcium/calmodulin-dependent protein kinase
II (CaM kinase II), an enzyme with a pivotal role in synaptic plasticity and cognitive
functions, has been implicated in the action of anticonvulsants, benzodiazepines,
and antidepressants, but little is known as to its role in the action of different
drugs employed for treatment of psychiatric disorders.
Methods:
We studied the function and expression of CaM kinase II following chronic treatment
of rats with two antidepressants, fluvoxamine and desipramine, a typical antipsychotic
drug, haloperidol, and the typical medication for manic-depressive disorder, lithium.
Results:
Antidepressants significantly increased the kinase activity in presynaptic vesicles
of frontal/prefrontal cortex. Haloperidol induced no change, whereas lithium significantly
decreased the activity. Kinase activation by antidepressants was further demonstrated
by increased phosphorylation of exogenously added recombinant synaptotagmin. Immunoreactivity
of vesicular kinase (α-isoform) was significantly increased by reuptake blockers but
not by the two other drugs. Kinetic analysis showed that limiting value of enzymatic
velocity (Vmax) of the kinase for substrate was also increased by reuptake blockers
and decreased by lithium; however, neither messenger ribonucleic acid nor protein
expression level of the kinase was increased in frontal/prefrontal cortex homogenates
of antidepressant-treated rats, suggesting the involvement of local synaptic mechanisms.
Conclusions:
These findings show that functional regulation of presynaptic CaM kinase II is selectively
affected by different psychotropic drugs, and suggest local synaptic mechanisms for
pharmacological regulation of the kinase.
Keywords
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Article info
Publication history
Accepted:
June 21,
2002
Received in revised form:
June 17,
2002
Received:
March 20,
2002
Identification
Copyright
© 2003 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
