Intranasal Leptin Prevents Opioid Induced Sleep Disordered Breathing in Obese Mice.

Intranasal Leptin Prevents Opioid Induced Sleep Disordered Breathing in Obese Mice. Am J Respir Cell Mol Biol. 2020 Jun 30;: Authors: Freire C, Pho H, Kim LJ, Wang X, Dyavanapalli J, Streeter SR, Fleury-Curado T, Sennes LU, Mendelowitz D, Polotsky VY Abstract Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to co-morbid obstructive sleep apnea. Naloxone, a μ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Similar to obese humans, diet-induced obese mice hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, diet-induced obese mice were treated with morphine at 10 mg/kg subcutaneously and with leptin vs placebo intranasally. Sleep and breathing were recorded by barometric plethysmography and pain sensitivity was measured by the tail flick test. Excitatory post-synaptic currents were recorded in vitro from hypoglossal motor neurons following application of the μ opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) and leptin. Morphine dramatically increased the frequency of apneas and greatly increased severity of hypoventilation and obstructive sleep apnea. Leptin dec...
Source: American Journal of Respiratory Cell and Molecular Biology - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research