Effect of combination of peripheral oxytocin and naltrexone at subthreshold doses on food intake, body weight and feeding-related brain gene expression in male rats

Oxytocin as an Anti-obesity Treatment

“…For instance, pre-clinical and clinical studies indicate that OT in combination with the opioid antagonist, naltrexone, is an effective strategy to reduce food intake (animals, humans) as well as body weight (humans). Peripheral (intravenous) administration of OT and naltrexone was recently found to be effective at reducing palatable 10% sucrose solutions as well as intake of a high fat/high sugar diet in rats ( Head et al, 2021 ). Intranasal OT was also found to be effective at reducing hyperphagia and maintaining weight loss when given in combination with the opioid antagonist, naltrexone, to a 13-year-old adolescent male with craniopharyngioma related hypothalamic obesity ( Hsu et al, 2017 ).…”

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

“…As shown in [ 15 ], IP and subcutaneous OT decreases various aspects of consumption at a standard dose of 1 mg/kg body weight (unlike opioid receptor antagonists whose effective doses are greatly dependent on palatability of food (e.g., [ 7 , 8 ])). In order to confirm that indeed the 1 mg/kg OT dose is sufficient to decrease consumption in our cohort of adolescent animals, we used the palatable high-fat high-sugar (HFHS) diet paradigm previously published in relation to OT’s effect on feeding [ 26 ].…”

“…Immediately after the treatment, they were given the HFHS diet and the consumption was measured 2 h later. It should be noted that the 2 h feeding period used in this and subsequent experiments was chosen based on the effective 2 h timeframe for the OT + NTX treatment published in the earlier report that focused on feeding responses in adult animals (hypophagia was found to be a short-lived phenomenon in that previous study) [ 26 ].…”

“…The case study by Hsu et al writes well into this hypothesis, though considering that the treatment was done in an adolescent in whom overeating developed as a result of the craniopharyngioma resection, there is a reasonable doubt that outcomes might differ in adolescents whose overeating is not driven by the prior surgical damage to the hypothalamus. We have recently reported that adult animals subjected to the combined OT + NTX treatment indeed eat less of the high-fat high-sugar diet presented right after the injection, but in that case, the experiments were performed in adult rather than adolescent rats [ 26 ]. Importantly, adolescents show heightened sensitivity to rewarding stimuli, including food [ 27 ].…”

“…Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas in response to the OT + NTX treatment. Similar to the previously published studies on OT and NTX in adult rats [ 26 ] in which a synergistic effect of the two molecules was anticipated, we used the doses of OT and NTX that—if administered alone—were subthreshold. This is because the ultimate goal of combination treatments is to use very low drug doses (well below the minimum effective doses in single drug treatment regimens) to minimize other (undesirable) effects of each compound.…”