Effect of naltrexone on feeding, neuropeptide y and uncoupling protein gene expression during lactation

Neuropeptide Y increases feeding and decreases measures of brown adipose tissue thermogenesis. In lactating rats, increased feeding, increased hypothalamic neuropeptide Y neuroactivity and decreased thermogenesis occur. Naltrexone is an opioid receptor antagonist which decreases neuropeptide Y-induced feeding and reverses neuropeptide Y-induced decreases in brown adipose tissue thermogenesis. We hypothesized that opioid receptors are involved in neuropeptide Y neuroactivity during lactation. To see if naltrexone would alter feeding, neuropeptide Y gene expression in the arcuate nucleus, neuropeptide Y levels in the paraventricular nucleus, and uncoupling protein gene expression in brown adipose tissue of lactating rats, osmotic minipumps pre-filled with either 0.9% saline or naltrexone (70 μg/h) were implanted subcutaneously in 47 female Sprague-Dawley rats weighing 309 ± 5 g. Half these rats were studied on days 10–16 of lactation, and the other half were studied 7 days after lactation. After 48 h, neuropeptide Y mRNA levels and uncoupling protein mRNA levels were determined using specific cDNA probes. Neuropeptide Y peptide levels in the paraventricular nucleus were measured by radioimmunoassay. Naltrexone decreased food intake by 26% in the post-lactating rats, but had no effect on feeding in the lactating animals. Lactation resulted in significantly increased arcuate neuropeptide Y mRNA, decreased neuropeptide Y levels in the paraventricular nucleus and decreased brown adipose tissue uncoupling protein mRNA levels. Naltrexone did not influence any of these parameters. Thus, the alterations in neuropeptide Y neuroactivity and brown fat thermogenesis which occur in lactation is not altered by generalized opioid receptor blockade.