Acute Tryptophan Depletion Reduces Nitric Oxide Synthase in the Rat Hippocampus

Abstract

Acute tryptophan depletion (ATD) is extensively used to investigate the role of central serotonin (5-HT). However, several studies reported that ATD had no significant effect on central 5-HT concentration and some ATD-induced changes was independent of 5-HT in the rodent brain. Therefore, the potential mechanism of ATD might not be ascribed solely to changes in the central 5-HT system. In recent studies, evidence suggests that nitric oxide synthase (NOS) is closely associated with ATD-induced changes in modulation of cerebral blood flow and metabolism, cognitive, and locomotor activity. Thus, NOS is implicated to be an underlying factor contributing to ATD-induced changes. In the present study, the effect of ATD upon central NOS levels in the rat was evaluated. Male Sprague-Dawley (SD) rats were orally administered a tryptophan-free protein-carbohydrate mixture. Then, ATD effects upon affective behavior and spatial memory were assessed by the forced swimming test (FST) and Morris water maze test, respectively. Further, NOS activity and neuronal NOS (nNOS) protein levels in the hippocampus were measured after ATD. Our experimental results showed that ATD had no influence on affective behavior in the FST or spatial memory in SD rats. Interestingly, a significant reduction of both constitutive NOS activity and nNOS protein levels after ATD was found in the hippocampus. These findings demonstrate ATD does not influence affective behavior and spatial memory despite a direct effect on hippocampal NOS. Our study might provide a valuable clue for exploring earlier reported ATD-induced behavioral and neurochemical changes in rodents.

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

“…Acute oral administration of a tryptophan-free protein-carbohydrate mixture to rats significantly lowered hippocampus tryptophan levels [ 70 ] and produced impaired performance in the visual working memory novel object recognition test [ 34 , 71 , 72 , 73 ], but not sustained attention [ 70 ] or spatial learning [ 71 , 74 ] tasks. In contrast, chronic tryptophan depletion, which simulates a long term reduction in central serotonin in brain regions including the hippocampus, frontal cortex, and striatum in rodents [ 75 ], impaired object-recognition memory [ 75 ] and hippocampal-dependent contextual fear memory [ 76 ].…”

Of rodents and humans: A comparative review of the neurobehavioral effects of early life SSRI exposure in preclinical and clinical research

“…Similarly, perinatal exposure to the tricyclic antidepressant clomipramine resulted in increased 5‐HT1a mRNA expression in the adult hippocampus (Limon‐Morales et al, 2014), and decreased presynaptic 5‐HT1a expression in the dorsal raphe (Zohar et al, 2015), likely a compensatory mechanism for lower 5‐HT production. Interestingly, a separate body of work showed that reducing 5‐HTergic tone via acute dietary tryptophan depletion is not enough to alter FST immobility or spatial memory in adult Sprague‐Dawley rats (Liu et al, 2013). When compared to studies that show inhibition of 5‐HT synthesis via parachlorophenylalanine during gestation increases despair behavior and impairs MWM performance in the adult animal (Vataeva et al, 2007), these findings suggest that timing of acute reductions in 5‐HT content may be necessary for changes in behavior.…”