Low tryptophan diet increases stress-sensitivity, but does not affect habituation in rats

Department of Psychiatry, University Medical Center Groningen, Graduate School of Behavioral Cognitive Neurosciences, University of Groningen, Groningen, The Netherlands.
Neurochemistry International (Impact Factor: 3.09). 02/2008; 52(1-2):272-81. DOI: 10.1016/j.neuint.2007.05.022
Source: PubMed


Cerebral dysfunction of 5-HT (serotonin) has been associated with stress response and with affective disorders. Stress alone is insufficient to induce depression, since only a minor proportion of subjects that have experienced stressful life events develop depressive episodes. We investigated whether long-term brain 5-HT depletion induced in rats by a diet with low content of its precursor tryptophan affects stress-responsiveness in rats. Stress-sensitivity was measured through various physiological parameters and by measuring the rats' response to acoustic stimuli. One group of rats was subjected to daily acoustic stimulus sessions for 5 days. Other groups received both immobilization stress and acoustic stimulus sessions daily for either 9 days (chronic experiment) or 1 day (acute experiment). A low tryptophan diet led to decreases in plasma tryptophan levels, low ratio of tryptophan/large neutral amino acid, whole blood 5-HT, and neuronal 5-HT content in the Dorsal and Median Raphe Nuclei, as well as altered c-fos expression in the brain. Without concomitant immobilization, the diet alone did not affect reactivity and habituation to acoustic stimuli, although plasma corticosterone levels, but not the adrenal weights, were increased on day 5. Low tryptophan and chronic immobilization stress together with the acoustic testing procedure increased adrenal weight, plasma corticosterone levels and reactivity to the acoustic stimuli, but not the rate of habituation to acoustic stimuli. These results show that cerebral dysfunction of serotonin achieved through a low tryptophan diet, increases the sensitivity of rats to external and stressful stimuli, but does not impair the capacity to adapt to these stimuli. Accordingly, brain-serotonin modulates reactivity to stress, but not stress coping.

Download full-text


Available from: Peter Johannes Van der Most
  • Source
    • "Therefore , the findings of Bosker et al. (2010) suggest a higher level of anxiety in the citalopram discontinuation group, which is similar to the increased incidence of anxiety in patients with the SSRI discontinuation syndrome. An increased reactivity to acoustic stimuli in rats has been linked to long-term depletion of serotonin in the brain (Tanke et al., 2008). Consistent with that notion, Bosker et al. (2010) found that an index of serotonin turnover [the ratio of 5-hydroxyindoleacetic acid to serotonin (5-HIAA/5-HT)] was increased after the 48-h washout period following chronic citalopram treatment, while chronic treatment exerted no significant effect on serotonin turnover. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Besides demonstrated efficacy, selective serotonin reuptake inhibitors (SSRIs) hold other advantages over earlier antidepressants such as greater tolerability and a wider range of clinical applications. However, there is a growing body of clinical evidence which suggests that SSRIs could, in some cases, be associated with a withdrawal reaction upon cessation of regular use. In addition to sensory and gastrointestinal-related symptoms, the somatic symptoms of the SSRI discontinuation syndrome include dizziness, lethargy, and sleep disturbances. Psychological symptoms have also been documented, usually developing within 1-7 days following SSRI discontinuation. The characteristics of the discontinuation syndrome have been linked to the half-life of a given SSRI, with a greater number of reports emerging from paroxetine compared to other SSRIs. However, many aspects of the neurobiology of the SSRI discontinuation syndrome (or SSRI withdrawal syndrome) remain unresolved. Following a comprehensive overview of the clinical evidence, we will discuss the underlying pathophysiology of the SSRI discontinuation syndrome and comment on the use of animal models to better understand this condition.
    Full-text · Article · Apr 2013 · Frontiers in Pharmacology
  • Source
    • "Such procedure has been used as a model of neonatal stress in both rats and mice (Catalani et al., 1993; Macrıèt al., 2007, 2009). Both treatments have independently been associated with behavioural, endocrine and anatomical alterations analogous to human depression in rodents (Uchida et al., 2005; Skorzewska et al., 2007; Tanke et al., 2008; Zhao et al., 2008; Zoratto et al., 2011). Animal facility reared dams with ad libitum access to "
    [Show abstract] [Hide abstract]
    ABSTRACT: The serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis are crucially involved in the regulation of emotions. Specifically, spontaneous and/or environmentally mediated modulations of the functionality of these systems early in development may favour the onset of depressive- and anxiety-related phenotypes. While the independent contribution of each of these systems to the emergence of abnormal phenotypes has been detailed in clinical and experimental studies, only rarely has their interaction been systematically investigated. Here, we addressed the effects of reduced serotonin and environmental stress during the early stages of postnatal life on emotional regulations in mice. To this aim, we administered, to outbred CD1 mouse dams, during their first week of lactation, a tryptophan deficient diet (T) and corticosterone via drinking water (C; 80μg/ml). Four groups of dams (animal facility rearing, AFR; T treated, T; C treated, C; T and C treated, TC) and their male offspring were used in the study. Maternal care was scored throughout treatment and adult offspring were tested for: anhedonia (progressive ratio schedule); anxiety-related behaviour (approach-avoidance conflict paradigm); BDNF, dopamine and serotonin concentrations in selected brain areas. T, C and TC treatments reduced active maternal care compared to AFR. Adult TC offspring showed significantly increased anxiety- and anhedonia-related behaviours, reduced striatal and increased hypothalamic BDNF and reduced dopamine and serotonin in the prefrontal cortex and their turnover in the hippocampus. Thus, present findings support the view that neonatal variations in the functionality of the serotonergic system and of HPA axis may jointly contribute to induce emotional disturbances in adulthood.
    Full-text · Article · May 2012 · Psychoneuroendocrinology
  • Source
    • "Indeed, Fadda et al. (2000) reported that, already after four days, a TRP-free diet induced an almost total disappearance of 5-HT extracellular levels in the frontal cortex. Similarly, Tanke et al. (2008) observed a marked decrease in blood 5-HT levels and neuronal 5-HT content on day 6 already. Accordingly, in our present experiment, we decided to wait for five days (after providing diets), thus starting operant protocols on the sixth day. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Psycho-genetic studies have revealed a role for the brain serotonin system in gambling proneness and poor decision-making. We assessed whether manipulation of brain serotonin levels in rats affected performance in operant-based tasks for decision-making and gambling proneness. Male Wistar rats were exposed to an l-tryptophan (TRP) deficient diet (0.0 g/kg; T- group) or to a control, l-tryptophan containing diet (2.8 g/kg; T+ group). The same rats were tested for decision-making performance in the rodent Iowa Gambling Task (rIGT) using home-cage operant panels, and subsequently for gambling proneness in a Probabilistic Delivery Task (rPDT) using classic Skinnerboxes. At sacrifice, monoamines and metabolites were evaluated with HPLC analysis, confirming a drastically reduced serotonin synthesis, as well as altered dopamine turnover in the prefrontal cortex of T- rats. As expected, control rats (T+) progressively chose the option with the best long-term payoff in the rIGT, and also shifted from "Large & Luck-Linked" (LLL) to "Small & Sure" (SS) reinforcers in the rPDT. In contrast, depleted animals (T-) exhibited a weaker improvement of performance in the rIGT and maintained a sub-optimal attraction for LLL reinforcer in the rPDT. Comparing individual performances in both tests, we found a significant correlation between the two tasks in control (T+) but not in depleted (T-) rats. The present study revealed that (1) brain 5-HT depletion leads to poor decision-making and to gambling proneness; (2) the relationship between these two traits, shown in the control group, was disrupted in 5-HT depleted rats. The data are discussed in terms of changes within forebrain loops involved in cognitive and motivational/affective processes.
    Full-text · Article · Nov 2011 · Neuropharmacology
Show more

We use cookies to give you the best possible experience on ResearchGate. Read our cookies policy to learn more.