Effects of dietary tryptophan variations on extracellular serotonin in the dorsal hippocampus of rats.

Rationale: There is evidence to suggest that the efficacy of selective serotonin reuptake inhibitors (SSRIs) in depression is dependent on the availability of serotonin (5-HT) in the brain. Moreover, there is circumstantial evidence suggesting that plasma tryptophan (TRP) levels can predict response to SSRIs. These findings suggest that dietary TRP variations may affect the efficacy of SSRI in major depression.

Objectives: To study the neurochemical and behavioral effects of dietary TRP variations in rats.

Methods: In vivo microdialysis in the hippocampus was performed in conscious rats randomly assigned to receive a diet containing low, normal or high levels of TRP. Basal levels of 5-HT and 5-HIAA were measured using HPLC. Fenfluramine and fluvoxamine were infused locally to determine the effect of the diet on 5-HT availability and release. In a parallel group of rats, the differential reinforcement of low rate 72 s (DRL-72 s) schedule was used to assess the behavioral effects of the dietary manipulations.

Results: 5-HT and 5-HIAA levels were significantly decreased after TRP low diet and 5-HT, but not 5-HIAA, levels were significantly increased after TRP high diet. 5-HT release after fluvoxamine and fenfluramine was significantly diminished in rats on a TRP low diet, and significantly enhanced after fenfluramine in rats on a TRP high diet. DRL-72 performance in rats was decreased by a TRP low diet, whereas a TRP high diet increased DRL performance similar to fluvoxamine administration.

Conclusion: The amount of 5-HT released after a 5-HT releasing agent and the effect of an SSRI on extracellular 5-HT are dependent on the nutritional availability of TRP. Moreover, increased availability of TRP affects behavior in a manner similar to SSRI administration. These findings suggest that nutritional factors have behavioral and neurochemical effects, relevant for the treatment of depression.