[Effects of chronic administration of antidepressants on microtubule assembly in rat cerebral cortex]

We examined the effects of chronic treatment with several types of antidepressants on microtubule assembly and phosphorylation of microtubule-associated proteins (MAPs) in the rat cerebral cortex. The microtubule assembly was monitored in turbidity at 350 nm using a spectrophotometer. Chronic but not acute treatment with desipramine (DMI), maprotiline (MPR) or citalopram (CTR) inhibited microtubule assembly, assayed in the presence of protein phosphatase inhibitors (PPI). In contrast, this inhibitory effect was completely nullified in the absence of PPI. The three compounds had no direct effect on microtubule assembly. The phosphorylation of MAPs (MAP2 and tau) was investigated by immunoblotting with monoclonal antibodies (phosphoserine, phosphothreonine and phosphotyrosine) after immunoprecipitation of MAPs. The serine but not threonine or tyrosine phosphorylation of MAP2 was significantly increased after chronic treatment with DMI, MPR or CTR. The phosphorylation of tau was not altered following chronic administration of antidepressants. These results suggest that the inhibition of microtubule assembly observed after chronic antidepressant treatment is attributable to an increase in the phosphorylated MAP2 and this effect may represent a novel and common action of typical and atypical antidepressant agents. Our results show that besides second messengers system, protein phosphorylation might be involved in the therapeutic effects of antidepressants.