Long-term voluntary exercise and the mouse hypothalamic-pituitary-adrenocortical axis: impact of concurrent treatment with the antidepressant drug tianeptine
by
Droste SK, Schweizer MC, Ulbricht S, Reul JM.
Max Planck Institute of Psychiatry,
Section of Neuropsychopharmacology,
Munich, Germany.
J Neuroendocrinol. 2006 Dec;18(12):915-25.

ABSTRACT

We investigated whether voluntary exercise and concurrent antidepressant treatment (tianeptine; 20 mg/kg/day; 4 weeks) exert synergistic effects on the mouse hypothalamic-pituitary-adrenocortical (HPA) axis. Animals had access to a running wheel, were treated with the antidepressant, or received both conditions combined. Control mice received no running wheel and no drug treatment. Exercise resulted in asymmetric changes in the adrenal glands. Whereas sedentary mice had larger left adrenals than right ones, this situation was abolished in exercising animals, mainly due to enlargement of the right adrenal cortex. However, antidepressant treatment alone was ineffective whereas the combination of antidepressant treatment and exercise resulted in an enlargement of both adrenal cortices. In these respective conditions, the levels of tyrosine hydroxylase (TH) mRNA expression in the left and right adrenal medullas varied greatly in parallel to the changes observed in the adrenal cortex sizes. TH mRNA expression in the locus coeruleus of exercising mice was significantly increased irrespective of concomitant tianeptine treatment. Corticotrophin-releasing factor mRNA levels in the hypothalamic paraventricular nucleus were decreased after voluntary exercise but were unaffected by tianeptine. Exercise, particularly in combination with tianeptine treatment, resulted in decreased early morning baseline plasma levels of corticosterone. If animals were exposed to novelty (i.e. a mild psychological stressor), a decreased response in plasma corticosterone levels was observed in the exercising mice. By contrast, after restraint, a mixed physical and psychological stressor, exercising mice showed an enhanced response in plasma corticosterone compared to the controls; a response which was even further boosted in exercising mice concomitantly treated with tianeptine. Under either condition, plasma adrenocorticotrophic hormone levels were not different between groups. Thus, voluntary exercise impacts substantially on HPA axis regulation. Concurrent tianeptine treatment results in synergistic actions, mainly at the adrenal level, affecting both its structure and function.

Tianeptine
Metabolism
Long-term use
Neuroplasticity
Serotonin/forebrain
Tianeptine (Stablon)
Tianeptine: structure
Melancholic depression
Antidepressant comparisons
Stress, memory and depression
Tianeptine for anxious depressives
Therapy-resistant major depression
Electrophysiological effects of tianeptine
Long-term trial of the antidepressant tianetine
Antidepressant comparisons: SSRIs v tianeptine
Tianeptine (Stablon) v paroxetine (Paxil, Seroxat)
Major depression treated with tianeptine (Stablon)

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