Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion

Abstract

. Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. Am J Physiol Regul Integr Comp Physiol 289: R1798 -R1806, 2005. First published September 8, 2005 doi:10.1152/ajpregu.00558.2005.-Laboratory mice drink little sucrose solution on initial exposure, but later develop a strong preference for sucrose over water that plateaus after a few days. Both the initial neophobia and later plateau of sucrose intake may involve central oxytocin (OT) signaling pathways. If so, then mice that lack the gene for OT [OT knockout (KO)] should exhibit enhanced initial and sustained sucrose intake compared with wild-type (WT) cohorts. To test this hypothesis, female OT KO and WT mice (11-13 mo old) were given a two-bottle choice between 10% sucrose and water available ad libitum for 4 days. On the first day, sucrose intake was 20-fold greater in OT KO mice compared with WT cohorts. The avid sucrose consumption by OT KO mice increased further on day 2 and was sustained at significantly higher levels than intake by WT mice. Enhanced initial and sustained sucrose intake also was observed in 5-to 7-mo-old male OT KO mice. The effect of genotype was observed over a range of sucrose concentrations and was maintained over at least 8 days of continual exposure. However, there was no effect of genotype on daily intake of sucroseenriched powdered chow. These findings indicate that the genetic absence of OT in mice is associated with enhanced initial and sustained intake of sucrose solutions. Thus central OT pathways may normally participate in limiting initial intake of novel ingesta and may also participate in limiting intake of sweet, highly palatable familiar ingesta.sugar; palatability; overeating; satiety RESULTS FROM STUDIES USING rats and mice support the view that oxytocin (OT) acts centrally to inhibit intake of food and other solutes (i.e., sodium chloride, NaCl, solution) under certain experimental conditions. For example, fasting-induced food intake is suppressed after central infusion of synthetic OT in rats (3, 27), and OT receptor blockade reduces the anorexic response to systemically administered hypertonic saline or to centrally infused corticotropin-releasing factor (26, 28, 39 -43). Similarly, dehydration anorexia is markedly attenuated in mice with an OT gene deletion [OT knockout (KO)] (36), and OT KO mice consume more NaCl solution than wild-type (WT) mice after overnight fluid deprivation (2) or after exposure to mild environmental stress (34). However, WT and OT KO mice ingest similar amounts of standard chow under ad libitum baseline conditions, after overnight food deprivation when drinking water is available, and after systemic administration of either cholecystokinin octapeptide or D-fenfluramine (18,36). These findings indicate that neurochemical systems other than OT are sufficient to limit or suppress food intake in mice under such conditions. OT neurons are activated by a variety of stressful and anxiogenic stimuli in rats (9,13,21,22,24,44,45) and mice (1,20,25)....

Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure

“…For example, peripheral activation of ␤ 3 -adrenergic receptors enhances central sensitivity to the anorexigenic hormone leptin (29). If oxytocin acts indirectly to reduce feeding via activation of the sympathetic nervous system, it would explain why animals lacking oxytocin receptor or deficient in oxytocin have normal food intake (1,9,19,51), whereas animals injected with oxytocin have reduced feeding and increased energy expenditure.…”

“…For example, low doses of intracerebroventricular oxytocin promote weight loss in rats without affecting feeding by elevating fat oxidation in adipose tissue, whereas higher doses of intracerebroventricular oxytocin both reduce feeding and increase lipolysis (11). Conversely, animals deficient in either oxytocin or its receptor show reduced energy expenditure, in some cases with normal feeding (1,9,19,51).…”

Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

“…This non-preference for novelty was in contrast to other paradigms using a preference for novelty to assess object recognition and episodic memory in mice and rats [17,22,32,70]. Neophobia for novel food, objects, or locations has been well-documented in rodents (see [23,31]), and can be altered by pharmacological challenge [6,26,76], rearing conditions [28], or genetic change [3,18,38,45,57,62]. Nonpreference for novelty has been shown to be strain-dependent in mice [26,34].…”

The Metabolic Regulator PGC-1α Directly Controls the Expression of the Hypothalamic Neuropeptide Oxytocin

“…Defects in oxytocin secretion were found to affect food intake and cause anorexia (Maejima et al, 2009;Zhang et al, 2011). Accordingly, knock-out of the oxytocin peptide causes increased intake of animals' selected diets (Amico et al, 2005;Kasahara et al, 2007;Miedlar et al, 2007). Similarly, neuronal inactivation of PGC-1␣ leads to increased food intake (Ma et al, 2010).…”