Tetraspan protein CD151: a common target of mood stabilizing drugs?

The latency in onset of antimanic and mood stabilizing effects of lithium suggest that long-term neuronal adaptations mediated by changes in gene expression may be important to the therapeutic action of lithium treatment. Using differential display-polymerase chain reaction, several novel, hitherto unexpected lithium-regulated genes have been isolated, all of which would not have been predicted with the candidate gene approach. During the process of characterizing one of these novel genes, we have identified a cDNA clone, a homolog of human/mouse transmembrane-4-superfamily (also known as tetraspan) protein, CD151, the expression of which was significantly decreased in rat frontal cortex following chronic (five weeks) lithium treatment. The reduction of CD151 mRNA levels was also observed following chronic administration of carbamazepine and valproate. Conversely, the expression of CD151 was not altered by short-term (one week) lithium treatment and by chronic administration of the tricyclic antidepressant, imipramine, or the typical antipsychotic, haloperidol, further demonstrating time dependence and pharmacological specificity of this effect. Our studies, thus, indicate that CD151 may represent a therapeutically relevant target common to lithium and the anticonvulsant mood stabilizing drugs, carbamazepine and valproate.