Serotonin and Norepinephrine Reuptake Inhibition and Eating Behavior

Abstract

Brain neurotransmitters, serotonin and norepinephrine, play an important role in the central nervous control of energy balance and are involved in symptomatology related to both obesity and depression. Therefore both serotonin and norepinephrine neural pathways have been paid a special attention as targets for the antiobesity drugs, antidepressants, and drugs used in the treatment of eating disorders. Selective serotonin reuptake inhibitors (SSRI) have been used in the treatment of depression and eating disorders but have failed to achieve sustained weight loss in the treatment of obesity. Sibutramine, a serotonin and norepinephrine reuptake inhibitor, which induces satiety and prevents decline in metabolic rate associated with a hypocaloric diet, is currently the sole centrally acting drug indicated for the long-term treatment of obesity. Depression, dietary disinhibition (evaluated by the Eating Inventory [EI]), and stress are associated with the accumulation of abdominal fat and the development of metabolic syndrome and related diseases. Subjects with abdominal obesity demonstrate neuroendocrine abnormalities which result in disturbances in hypothalamo-pituitary-adrenal (HPA) function. Treatment with SSRI might interrupt the vicious circle which leads to endocrine abnormalities and the accumulation of abdominal fat. Obesity treatment with sibutramine results, not only in significant weight loss, but also in reduction of abdominal fat and in the improvement of health risks associated with metabolic syndrome (lipid profile, blood glucose, insulin, HbA1c, and uric acid), as well as in the decline in disinhibition score of the EI. In a 1-year sibutramine trial, only a decrease in the disinhibition score remained a significant correlate of weight loss among the psychobehavioral and nutritional factors which were taken into account.

Variations in tryptophan hydroxylase 2 linked to decreased serotonergic activity are associated with elevated risk for metabolic syndrome in depression

“…Furthermore, direct effects of the serotonergic system or an interaction with the HPA axis 64,65 could explain the interrelationship of MetS and MD. In fact, several studies indicate an interaction of glucocorticoids and TPH2 or its functional genetic variants, respectively.…”

“…29,30,63 Furthermore, the serotonergic system has been shown to be involved in appetite and weight regulation and to modify the risk for metabolic disorders, as previous studies reported reduced CSF serotonin levels and decreased CNS serotonergic responsivity in MetS and obesity. 26,28 On the other hand, treatment with SSRIs decreases appetite and induces weight loss, 25,64 suggesting that dysregulation in central serotonergic system is important in obesity and MetS.…”

La double vie de la sérotonine ou quand la génétique découvre la physiologie

“…Comme tout bon médicament, les ISRS ne sont pas dépourvus d'effets secondaires. L'un d'entre eux est de provoquer une perte osseuse chez les patients traités au long cours, l'autre est d'augmenter l'appétit [16][17][18][19]. Ces observations cliniques suggèrent que la sérotonine d'origine cérébrale pouvait bien être un régulateur de la masse osseuse et de l'appétit.…”

Absence of sibutramine effect on spontaneous anxiety in rats

“…On the other hand, nontriclyclic agents, such as selective serotonin (SSRI) and serotonin-noradrenaline (SNRI) reuptake inhibitors, have been preferred for use in the treatment of anxiety and depression, but have failed to achieve sustained weight loss in the treatment of obesity (1,(13)(14)(15). Despite this, as with sibutramine, SSRIs and SNRIs have also increased locomotion (16,17).…”

“…Thus, both neurotransmitter pathways have been given special attention as antiobesity and antidepressant agents (1).…”