We have investigated the effects of lithium treatment on cAMP-dependen
t protein kinase in discrete brain areas of rat by using photoaffinity
labeling as well as western blotting. Lithium administered for 5 week
s resulted in a significant increase of the cAMP binding to the 52 kDa
cAMP-receptor in the soluble, but not in the particulate, fractions o
f both hippocampus and frontal cortex. Moreover, immunoblotting experi
ments revealed that chronic lithium treatment significantly increased
the immunoreactivity against the regulatory and the catalytic subunits
of the cAMP-dependent protein kinase in the soluble fraction of both
brain areas. In contrast, no appreciable effect was observed in the pa
rticulate functions. Short-term lithium treatment induced a significan
t increase in the immunolabeling of the catalytic subunits in the solu
ble fraction of both areas; whereas, the regulatory subunits and the a
ctin were unchanged. In the particulate fractions, short-term lithium
treatment did not elicit any substantial modification. Taken together,
the results of the present study add to the growing evidence indicati
ng that components of the cAMP signalling could play a crucial role in
the biochemical action of lithium. (C) 1998 American College of Neuro
psychopharmacology. Published by Elsevier Science Inc.