Moderate dieting causes 5-HT _2C receptor supersensitivity

Abstract

SynopsisDieting is a widespread behaviour in developed countries, which in predisposed individuals can lead to the development of clinical eating disorders such as bulimia nervosa and anorexia nervosa. We studied the effect of moderate dieting in healthy women on the prolactin response to the serotonin (5-HT) receptor agonist, m-chlorophenylpiperazine (mCPP), a measure of the sensitivity of post-synaptic 5-HT2C receptors. Dieting significantly increased the prolactin response to mCPP and lowered plasma concentrations of the 5-HT precursor, tryptophan. We propose that dieting in women is associated with the development of functional supersensitivity of 5-HT2C receptors, probably in response to lowered levels of brain 5-HT. Alterations in brain 5-HT neurotransmission could play a part in dieting-induced dysregulation of eating and the development of clinical eating disorders in predisposed individuals.

Escitalopram Enhances the Association of Serotonin-1A Autoreceptors to Heteroreceptors in Anxiety Disorders

“…5-HT 1A autoreceptors inhibit tonic firing activity of serotonergic neurons (Hajos et al, 2001;Evans et al, 2008) and hence decrease 5-HT release into the synaptic cleft (Parsons et al, 2001;Bundgaard et al, 2006). Additional studies reported inverse relationships between serotonin synthesis and heteroreceptor binding (Frey et al, 2008) and behavioral responses (Cowen et al, 1996;Heslop and Curzon, 1999). This suggests that low synaptic 5-HT levels, caused by a high level of 5-HT 1A autoreceptors, lead to a compensatory upregulation of 5-HT 1A heteroreceptors.…”

A history of caloric restriction induces neurochemical and behavioral changes in rats consistent with models of depression

“…With respect to mood regulation, dysregulated or reduced 5-HT activity contributes to mood disturbances, particularly depression (Jimerson, et al, 1990;Ressler and Nemeroff, 2000;Wurtman and Wurtman, 1995). Clinical studies reveal associations between caloric restriction and 5-HT disruption (Anderson, et al, 1990;Cowen, et al, 1996;Goodwin, et al, 1987;Walsh, et al, 1995), especially in individuals with eating disorders that typically have HCR and suffer mood disturbances such as anxiety (Godart, et al, 2004;Kaye, et al, 2004;Keel, et al, 2005;Sassaroli, et al, 2005) and depression (Keel, et al, 2005;Mora-Giral, et al, 2004;Patton, et al, 1997;Stice, et al, 2004). Despite these clinical observations, possible associations between altered 5-HT function and caloric restriction have not been studied in animal models of eating or emotional disorders.…”

Stress and hunger alter the anorectic efficacy of fluoxetine in binge‐eating rats with a history of caloric restriction

“…As in humans, food restriction in animals generally decreases serum and CNS 5-HT levels, which may be linked to a decrease in diet-derived tryptophan available for 5-HT synthesis (Chik, Ho, & Brown, 1986;Cowen, Clifford, Walsh, Williams, & Fairburn, 1996;Haleem & Haider, 1996;Kohsaka, Takamatsu, & Tsukada, 1980).…”