Chronic treatment with mood stabilizers increases membrane GRK3 in rat frontal cortex

Area of Science:

• Neuropharmacology
• Molecular Psychiatry
• Signal Transduction

Background:

• G-protein receptor kinases (GRKs) regulate G-protein coupled receptor (GPCR) desensitization.
• Altered GRK activity may contribute to GPCR supersensitivity observed in affective disorders.

Purpose of the Study:

• To investigate the effects of chronic lithium, carbamazepine, and valproate on GRK2 and GRK3 protein levels in rat frontal cortex.
• To determine if these mood stabilizers influence GRK translocation.

Main Methods:

• Immunoblotting was used to quantify GRK2 and GRK3 protein levels.
• Rats were administered chronic, therapeutically relevant doses of lithium, carbamazepine, or valproate.
• Protein fractions were analyzed for membrane and cytosol localization.

Main Results:

• Lithium and carbamazepine significantly increased GRK3 protein in membrane fractions.
• The membrane-to-cytosol ratio of GRK3 was elevated by lithium and carbamazepine.
• Valproate did not affect GRK3 levels, and GRK2 remained unchanged by all treatments.

Conclusions:

• Chronic lithium and carbamazepine promote GRK3 translocation to the membrane in rat frontal cortex.
• This mechanism may counteract GPCR supersensitivity implicated in bipolar disorder.
• Valproate does not appear to modulate GRK3 levels or localization.