GAP-43 PHOSPHORYLATION BY PKC IN RAT CEREBROCORTICAL SYNAPTOSOMES - EFFECT OF ANTIDEPRESSANTS

Recent evidence, including our previous work, indicates that changes i n both c-AMP and phospholipid-dependent protein kinases (PKA and PKC) may be involved in neuroadaptive mechanisms occurring in brain after r epeated administration of antidepressants. The purpose of this study w as to examine the phosphorylation of a major PKC substrate involved in modulation of neurotransmitter release, GAP-43, in a synaptosomal pre paration from rat cerebral cortex after repeated administration of flu oxetine (FL) and desipramine (DMI). Groups of male rats were treated f or 21 days with either FL (5 mg/kg/day, i.p.), DMI (10 mg/kg/day, i.p. ) or vehicle (controls) and cortical synaptosomes were prepared 48 h o r 24 h after the last injection. Synaptosomal membrane proteins were r esolved by SDS-PAGE. Western immunoblotting and immunoprecipitation wi th anti-GAP-43 antibody have identified the GAP-43 protein as a single distinct band of apparent molecular weight of 56 kDa. The extent of p hosphorylation of GAP-43 protein by native PKC in synaptosomes of rats treated with either FL or DMI was not significantly different from th at observed in control animals. The previously observed suppression of basal PKC activity in rat cortical synaptosomes by FL and DMI treatme nt was thus not reflected in altered GAP-43 phosphorylation. It is thu s unlikely that changes in GAP-43 phosphorylation are involved in anti depressant-induced modulation of 5-HT release.