Clin Psychopharmacol Neurosci.  2012 Apr;10(1):25-33.

Altered Neuronal Markers Following Treatment with Mood Stabilizer and Antipsychotic Drugs Indicate an Increased Likelihood of Neurotransmitter Release

Affiliations
  • 1Department of Psychiatry, Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Melbourne Brain Centre, The University of Melbourne, Parkville, Australia. elscarr@unimelb.edu.au

Abstract


OBJECTIVE
Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effects of these drugs on neuronal markers previously reported to be altered in subjects with psychiatric disorders.
METHODS
Male Sprauge-Dawley rats were treated with vehicle (ethanol), lithium (25.5 mg per day), haloperidol (0.1 mg/kg), olanzapine (1.0 mg/kg) or a combination of lithium and either of the antipsychotic drugs for 28 days. Levels of cortical synaptic (synaptosomal associated protein-25, synaptophysin, vesicle associated protein and syntaxin) and structural (neural cell adhesion molecule and alpha-synuclein) proteins were determined in each treatment group using Western blots.
RESULTS
Compared to the vehicle treated group; animals treated with haloperidol had greater levels of synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.05), those treated with olanzapine had greater levels of synaptophysin (p<0.01) and syntaxin (p<0.01). Treatment with lithium alone did not affect the levels of any of the proteins. Combining lithium and haloperidol resulted in greater levels of synaptophysin (p<0.01), synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.01). The combination of lithium and olanzapine produced greater levels of synaptophysin (p<0.01) and alpha-synuclein (p<0.05).
CONCLUSION
Lithium alone had no effect on the neuronal markers. However, haloperidol and olanzapine affected different presynaptic markers. Combining lithium with olanzapine additionally increased alpha-synuclein. These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.

Keyword

Lithium; Antipsychotic agents; Nerve tissue proteins; SNARE proteins; Neural cell adhesion molecules

MeSH Terms

alpha-Synuclein
Animals
Antipsychotic Agents
Benzodiazepines
Cell Adhesion
Cell Proliferation
Haloperidol
Humans
Lithium
Male
Nerve Tissue Proteins
Neural Cell Adhesion Molecules
Neurons
Neurotransmitter Agents
Proteins
Qa-SNARE Proteins
Rats
SNARE Proteins
Synaptophysin
Antipsychotic Agents
Benzodiazepines
Haloperidol
Lithium
Nerve Tissue Proteins
Neural Cell Adhesion Molecules
Neurotransmitter Agents
Proteins
Qa-SNARE Proteins
SNARE Proteins
Synaptophysin
alpha-Synuclein
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