Selective effects of long-term lithium and carbamazepine administration on G-protein subunit expression in rat brain

The efficacy of lithium and carbamazepine in treatment of bipolar affective disorder is well established. Although a number of biochemical effects have been found the exact molecular mechanisms underlying their therapeutic actions have not been elucidated. Nor have the target regions in the brain been located. The objectives of the present investigation were to identify the selective effects and target regions of long-term treatment, with either lithium or carbamazepine, on G-protein subunit expression in rat brain. Effects were measured in hippocampus, hypothalamus, amygdala, frontal cortex, neostriatum, thalamus, raphe nuclei and cerebellum. At the protein level amounts of G alpha(o) decreased significantly (P < 0.01) in neostriatum and G beta increased in frontal cortex in response to both drug treatments. At the mRNA level amounts of G alpha(il) increased significantly (P < 0.01) in neostriatum. G alpha(s) messenger amounts decreased in frontal cortex and increased in thalamus. These effects were common for both drugs, however, in addition also some differential effects, specific for either of the two drugs, were observed. We conclude frontal cortex and neostriatum are important target regions of long-term treatment with either lithium or carbamazepine and suggest G alpha(o), G alpha(s), G alpha(il) and G beta to be selective target molecules. (C) 1998 Elsevier Science B.V.