Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 392, 241-251

Effects of Chronic Oxytocin Administration and Diet Composition on Oxytocin and Vasopressin 1a Receptor Binding in the Rat Brain

Affiliations

Effects of Chronic Oxytocin Administration and Diet Composition on Oxytocin and Vasopressin 1a Receptor Binding in the Rat Brain

Sara M Freeman et al. Neuroscience.

Abstract

Oxytocin (OT) elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates, and humans, in part, by reducing food intake. Chronic OT administration produces more sustained weight loss in high-fat diet (HFD)-fed DIO rodents relative to chow-fed controls, but the reasons for this effect remain unclear. We hypothesized that HFD-induced obesity is associated with elevated OT receptor (OXTR) binding in brain regions where OT is known to cause decreased food intake and that this sensitized neural system is one mechanism by which OT preferentially elicits weight loss in DIO rodents. We therefore determined the impact of diet (HFD vs chow) and drug treatment (chronic OT infusion vs vehicle) on (1) OXTR binding in hindbrain and forebrain sites where OT suppresses food intake relative to control sites that express OXTR and (2) forebrain vasopressin 1a receptor (AVPR1a) density to evaluate the specificity of any OT effects. Using quantitative receptor autoradiography, we found that (1) diet composition failed to alter OXTR or AVPR1a binding; (2) chronic OT treatment produced largely global reductions in forebrain OXTR and AVPR1a binding without significantly altering hindbrain OXTR binding. These findings suggest that forebrain OXTR and AVPR1a are down-regulated in response to chronic OT treatment. Given that chronic intranasal OT may be used as a therapeutic strategy to treat obesity, future studies should consider the potential downregulatory effect that chronic treatment can have across forebrain and hindbrain nonapeptide receptors and assess the potential contribution of both receptor subtypes to the outcome measures.

Keywords: food intake; obesity; oxytocin; receptor autoradiography.

Figures

Figure 1.
Figure 1.. Optical binding density of OXTR from the hindbrain following chronic 3V OT and vehicle infusions in rats that were fed a high fat diet (HFD) or chow.
Data are expressed as mean ± SEM (n=2–6 rats per group). *P<0.05 HFD vs. chow.
Figure 2.
Figure 2.. Optical binding density of OXTR binding from the forebrain following chronic 3V OT and vehicle infusions in rats that were fed a high fat diet (HFD) or chow.
Data are expressed as mean ± SEM (n=6–9 rats per group). *P<0.05 HFD vs. chow.
Figure 3.
Figure 3.. Representative autoradiograms of forebrain OXTR binding in saline (A,C,E) and OT (B,D,F) treated rats.
A,B. Full coronal sections at the level of the ventromedial hypothalamus (VMH), arcuate nucleus (ARC), and central amygdala (CeA), with white boxes indicating the zoomed in regions in panels C-F. C,D. Digitally zoomed images of the hypothalamus showing reduced OXTR binding after OT treatment (D) compared to saline (C). E,F. Digitally zoomed images of the amygdala showing reduced OXTR binding after OT treatment (F) compared to saline (D).
Figure 4.
Figure 4.. Optical binding density of AVPR1a binding from the forebrain following chronic 3V OT infusions in rats that were fed a high fat diet (HFD) or chow.
Data are expressed as mean ± SEM (n=7–9 rats per group). *P<0.05 HFD vs. chow.
Figure 5.
Figure 5.. Representative autoradiograms of forebrain AVPR1a binding in saline (A,C,E) and OT (B,D,F) treated rats.
A,B. Full coronal sections at the level of the ventromedial hypothalamus (VMH), arcuate nucleus (ARC), and central amygdala (CeA), with white boxes indicating the zoomed in regions in panels C-F. C,D. Digitally zoomed images of the hypothalamus showing reduced AVPR1a binding after OT treatment (D) compared to saline (C). E,F. Digitally zoomed images of the amygdala showing no change in AVPR1a binding between saline treated (E) and OT treated (F) rats.

Similar articles

See all similar articles

Cited by 3 articles

Publication types

Feedback