Antipsychotics affect multiple calcium calmodulin dependent proteins

Area of Science:

• Neuroscience
• Molecular Biology
• Pharmacology

Background:

• Calcineurin, a calmodulin-dependent phosphatase, is implicated in schizophrenia and antipsychotic treatment.
• Evidence suggests antipsychotics and schizophrenia may affect the broader calmodulin (CaM) signaling axis.

Purpose of the Study:

• To investigate the effects of psychoactive drugs on CaM, calmodulin-dependent protein kinases (CaMK), and calcineurin.
• To determine if antipsychotics specifically target CaM signaling proteins.

Main Methods:

• Western blotting
• In situ hybridization
• Immunocytochemistry
• Treatment of Sprague-Dawley rats with haloperidol, clozapine, risperidone, raclopride, amphetamine, lithium, valproic acid, and fluoxetine.

Main Results:

• Repeated antipsychotic treatment increased CaM and CaMII mRNA but decreased CaMKIV, CaMKKalpha, CaMKKbeta, and calcineurin protein levels in rat striatum.
• These decreases were transient, with protein levels reversing 24 hours post-treatment.
• Raclopride mimicked antipsychotic effects, while amphetamine increased these proteins.
• Mood stabilizers and fluoxetine had minimal effects, except for lithium increasing CaMKKbeta.

Conclusions:

• Antipsychotics specifically target multiple proteins within the CaM signaling pathway.
• The findings suggest a more complex interaction between antipsychotics, schizophrenia, and CaM signaling than previously understood.