Naltrexone is an opioid receptor antagonist approved for the treatment of alcohol and opioid use disorders at doses of 50-150 mg/d. Naltrexone has also been prescribed at much lower doses (3-6 mg/d) for the off-label treatment of inflammation and pain. Currently, a compelling mechanistic explanation for the reported efficacy of low-dose naltrexone (LDN) is lacking and none of the proposed mechanisms can explain patient reports of improved mood and sense of well-being. Here, we examined the possibility that LDN might alter the activity of the endogenous opioid system involving proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) in male and female mice. Known actions of POMC neurons could account for changes in pain perception and mood. However, using electrophysiologic, imaging and peptide measurement approaches, we found no evidence for such a mechanism. LDN did not change the sensitivity of opioid receptors regulating POMC neurons, the production of the β-endorphin precursor Pomc mRNA, nor the release of β-endorphin into plasma. Spontaneous postsynaptic currents (sPSCs) onto POMC neurons were slightly decreased after LDN treatment and GCaMP fluorescent signal, a proxy for intracellular calcium levels, was slightly increased. However, LDN treatment did not appear to change POMC neuron firing rate, resting membrane potential, nor action potential threshold. Therefore, LDN appears to have only slight effects on POMC neurons that do not translate to changes in intrinsic excitability or baseline electrical activity and mechanisms beyond POMC neurons and altered opioid receptor sensitivity should continue to be explored.
Pubmed ID: 34031099 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsA software tool which provides a means to acquire and analyze time-series data, as well as a direct route to publication quality graphics. It provides a variety of graph styles and automated, extended, and/or customizable analyses.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentions