We studied the effects of the multi-modal antidepressant, vortioxetine and the SSRI, paroxetine on pineal melatonin and monoamine synthesis in a sub-chronic tryptophan (TRP) depletion model of depression based on a low TRP diet.
Female Sprague-Dawley rats were randomised to groups a) control, b) low TRP diet, c) low TRP diet + paroxetine and d) low TRP diet + vortioxetine. Vortioxetine was administered via the diet (0.76 mg/kg of food weight) and paroxetine via drinking water (10 mg/kg/day) for 14 days.
Both drugs resulted in SERT occupancies > 90%. Vortioxetine significantly reversed TRP depletion-induced reductions of pineal melatonin and serotonin (5-HT) and significantly increased pineal noradrenaline NA. Paroxetine did none of these things.
Other studies suggest pineal melatonin synthesis may involve N-methyl-D-aspartate (NMDA) receptors and glutamatergic modulation. Here observed changes may be mediated via vortioxetine's strong 5-HT reuptake blocking action together with possible additional effects on glutamate neurotransmission in the pineal via NMDA receptor-modulation and possibly with added impetus from increased NA output.