School of Life Sciences, Oxford Brookes University, UKFulltext PDF
Study looks at effects of acute TRP loading on TRP metabolism in TRP depleted male and female rats. Sprague-Dawley rats were fed a low TRP diet for 0 (control), 6, 14 and 21 days. Animals were then loaded (ip) with TRP solution (80 mg/kg) one hour prior to being sacrificed. Procedures were carried out between 08.00 to 10.00 hours to reduce effects of estrus in females. TRP depletion directly enhanced the effect of TRP loading on plasma TRP, brain TRP, 5-HT, 5-HIAA and DA in male rats. Enhancements increased synchronously with the length of dietary period. In females, only plasma and brain TRP were similarly enhanced but brain 5-HT and 5-HIAA remained unchanged or reduced. In females, brain DA was similar to control across dietary periods. Results suggest an impairment of the TRP metabolic pathway in female rats only. Findings increase evidence differentiating male and female rats in terms of TRP metabolism and 5-HT neurotransmission and may suggest an area of potential treatment-resistance. Increases in DA may increase euphoria and decrease depression-like state in male rats only? Our recent evidence suggests that changes in inflammatory cytokines and HPA alter hepatic TRP/kynurenic metabolism which may indirectly affect central glutamate neurotransmission and end-point depression-like behavior in this model of depression. Our most recent results show that the multi-modal antidepressant, vortioxetine reversed TRP depletion-induced behavioral change in the FST and biomarkers of treatment resistance in female rats whereas paroxetine did not. Overall, alternative treatments may be more effective in women with treatment-resistant depression than in men.
Depression; Tryptophan depletion model; Gender; Estradiol; Tryptophan metabolic pathway
Franklin M. Effects of Gender in Rat Models of Depression: Acute Tryptophan Loading in Chronically Tryptophan-Depleted Rats Some New Old Data. Ann Psychiatr Clin Neurosci. 2020; 3(3): 1035.