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Altered neuronal markers following treatment with mood stabilizer and antipsychotic drugs indicate an increased likelihood of neurotransmitter release.

Scarr E, Dean B - Clin Psychopharmacol Neurosci (2012)

Bottom Line: Treatment with lithium alone did not affect the levels of any of the proteins.Lithium alone had no effect on the neuronal markers.These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Melbourne Brain Centre, The University of Melbourne, Parkville, Australia.

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.

No MeSH data available.


Related in: MedlinePlus

A schematic representation of the changes in neuronal markers following treatment with antipsychotics, either alone or in combination with lithium. Each treatment is colour coded and the arrows indicate the direction of change in the level of that marker following the specific regimen. SNAP-25, synaptosomal associated protein-25; NCAM-140, neural cell adhesion molecule 140.
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Figure 2: A schematic representation of the changes in neuronal markers following treatment with antipsychotics, either alone or in combination with lithium. Each treatment is colour coded and the arrows indicate the direction of change in the level of that marker following the specific regimen. SNAP-25, synaptosomal associated protein-25; NCAM-140, neural cell adhesion molecule 140.

Mentions: This study has shown that treatment with antipsychotic drugs alone or in conjunction with the archetypal mood stabilizer lithium has complex effects on markers of neurotransmitter release and structural proteins (Fig. 2).


Altered neuronal markers following treatment with mood stabilizer and antipsychotic drugs indicate an increased likelihood of neurotransmitter release.

Scarr E, Dean B - Clin Psychopharmacol Neurosci (2012)

A schematic representation of the changes in neuronal markers following treatment with antipsychotics, either alone or in combination with lithium. Each treatment is colour coded and the arrows indicate the direction of change in the level of that marker following the specific regimen. SNAP-25, synaptosomal associated protein-25; NCAM-140, neural cell adhesion molecule 140.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569157&req=5

Figure 2: A schematic representation of the changes in neuronal markers following treatment with antipsychotics, either alone or in combination with lithium. Each treatment is colour coded and the arrows indicate the direction of change in the level of that marker following the specific regimen. SNAP-25, synaptosomal associated protein-25; NCAM-140, neural cell adhesion molecule 140.
Mentions: This study has shown that treatment with antipsychotic drugs alone or in conjunction with the archetypal mood stabilizer lithium has complex effects on markers of neurotransmitter release and structural proteins (Fig. 2).

Bottom Line: Treatment with lithium alone did not affect the levels of any of the proteins.Lithium alone had no effect on the neuronal markers.These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Rebecca L. Cooper Research Laboratories, The Mental Health Research Institute, Melbourne Brain Centre, The University of Melbourne, Parkville, Australia.

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.

No MeSH data available.


Related in: MedlinePlus