Sleep is increased by liraglutide, a glucagon-like peptide-1 receptor agonist, in rats

• Published in: Brain research bulletin Vol. 192; pp. 142 - 155
• Main Authors: Fang, Jidong, Miller, Patti, Grigson, Patricia S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023
• Subjects: Addiction; adults; agonists; Animals; brain; EEG Slow Wave Activity; Electroencephalography; eyes; fentanyl; Glucagon-like peptide-1; Glucagon-Like Peptide-1 Receptor; heroin; Humans; Liraglutide; Liraglutide - pharmacology; Male; males; narcotics; obesity; Rats; scotophase; Sleep; subcutaneous injection; Wakefulness; EEG Slow Wave Activity; Glucagon-like peptide-1; Sleep; Addiction; Liraglutide
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2022.11.012

Sleep disturbances are prominent in drug use disorders, including those involving opioids in both humans and animals. Recent studies have shown that administration of liraglutide, a glucagon-like peptide-1 agonist, significantly reduces heroin taking and seeking in rats. In an effort to further understand the action of this substance on physiological functions and to evaluate safety issues for its potential clinical use, the aim of the present study was to determine whether the dose of liraglutide found effective in reducing responding for an opioid also could improve sleep in drug-naïve rats. Using a within-subjects design, adult male rats chronically implanted with EEG and EMG electrodes received subcutaneous injection of saline or 0.06, 0.10, 0.30 or 0.60 mg/kg liraglutide. The 0.10 and 0.30 mg/kg doses are known to be most effective in reducing responding for heroin in rats at light or dark onset during a 12:12 h light-dark cycle (0.10 mg/kg for taking and seeking, 0.30 mg/kg for seeking). EEG and EMG were recorded across the 24 h period following each injection. After both dark and light onset injections, liraglutide dose-dependently decreased wakefulness and increased non-rapid eye movement (NREM) sleep except at the lowest dose. The bout length of wakefulness and NREM sleep were decreased and increased, respectively. Whether administered at light or dark onset, the above alterations occurred primarily during the dark period (i.e., during the active period). The animals’ body weight was decreased after liraglutide treatments as expected since it is clinically used for the treatment of obesity. These data indicate that liraglutide, at doses known to reduce responding for heroin and fentanyl, also increases NREM sleep, suggesting that the increase in sleep may contribute to the protective effects of liraglutide and may promote overall general health. •Liraglutide dose-dependently increased NREM sleep during the dark period either after light or dark onset injection.•Liraglutide decreased EEG slow wave activity during NREM sleep, possibly as a secondary result of reduced wakefulness.•The sleep-promoting effects of liraglutide may enhance its anti-addiction effects and overall health in the same dose range.