Acute Hypophagia and Changes in c-Fos Immunoreactivity in Adolescent Rats Treated with Low Doses of Oxytocin and Naltrexone.

Mitchell A Head,Laura K Mccoll,Anica Klockars,Pawel K Olszewski,Allen S Levine

doi:10.3390/jcm11010059

Abstract

A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.

Highlights

One third of American children and adolescents are overweight or obese [1]
We examined whether NTX or OT + NTX affect feeding induced by energy needs, i.e., intake of standard chow following overnight food deprivation
Administration of 1 mg/kg OT in non-deprived animals given episodic access to the high-fat high-sugar (HFHS) produced a decrease in consumption (F(3, 27) = 4.34; p = 0.044; d = 1.46), whereas lower doses of the peptide were ineffective in reducing food intake (Figure 1)

Summary

Introduction

One third of American children and adolescents are overweight or obese [1]. In 2017, Hsu and colleagues published exciting results of a case study involving an adolescent male with craniopharyngioma resection-induced hypothalamic obesity and loss-of-control overeating. The authors initially treated the patient with intranasal OT to in order to lower food intake and body weight [3]. Following 10 weeks of the OT-alone administration, they expanded the treatment by co-administering OT with an opioid receptor antagonist, naltrexone (NTX). They found OT alone to be effective at reducing body weight and overeating, the adjunctive OT + NTX therapy promoted more robust changes in appetite and BMI

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Discussion

Conclusion