Further Electrochemical and Behavioural Evidence of a Direct Relationship Between Central 5-HT and Cytoskeleton in the Control of Mood



Francesco Crespi*
Biology Department, Neurosciences CEDD GlaxoSmithKline, Medicines Research Centre, via Fleming 4, 37135 Verona, Italy


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© Francesco Crespi; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Biology Department, Neurosciences CEDD GlaxoSmithKline, Medicines Research Centre, via Fleming 4, 37135 Verona, Italy; Tel +390458218707; E-mail: Francesco.M.Crespi@GSK.com


Abstract

Reduced activity of CNS serotonin is reported in unipolar depression and serotonin is the major target of recent antidepressant drugs. However, an acute depletion of serotonin in healthy individuals does not induce depressive symptoms suggesting that depression does not correlate with the serotonin system only. Neuronal plasticity (structural adaptation of neurons to functional requirements) includes synthesis of microtubular proteins such as tyrosinated isoform of α-tubulin and presence of serotonin as regulator of synaptogenesis. In depression neuronal plasticity is modified.

Here, in rats submitted to a behavioural test widely used to predict the efficacy of antidepressant drugs (forced swimming test: FST) a significant decrease of both cerebral tyrosinated α-tubulin expression and serotonin levels is monitored. Moreover, treatment with para-chlorophenylalanine (PCPA, compound that specifically depletes brain serotonin) but not alpha-methyl para tyrosine (α-MPT, compound that blocks synthesis of catechols: chemicals also implicated in depression) significantly reduced tyrosinated α-tubulin. Thus, a direct relationship between serotonin and tyrosinated α-tubulin appears to be present both in “physiological” and in “pathological” states. In addition, data obtained in animals submitted to FST and/or treated with the selective serotonin reuptake inhibitor (SSRI) fluoxetine further support the interrelationship between central serotonin and cytoskeleton. These data propose that direct relationship between serotonin and tyrosinated α-tubulin could be considered within the mechanism(s) involved in the pathogenesis of depression.

Keywords: Rat brain, monoamines, serotonin, microtubules, tyrosinated α-tubulin.