GLP-1 agonist liraglutide decreases operant methamphetamine intake in rats under conditions of short- but not extended-access to the drug

Objective Glucagon-like peptide-1 (GLP-1) receptor agonists have emerged as a therapeutic strategy for reducing drug craving and intake. However, their efficacy in methamphetamine use disorder remains unexplored. This study assessed the effects of repeated liraglutide treatment on methamphetamine intravenous self-administration in rats. Methods Male Wistar rats were trained to self-administer methamphetamine in either short- (1.5-h) or extended- (6-h) access sessions. Once a stable level of drug intake was achieved, the animals received daily subcutaneous injections of liraglutide (0.1 mg/kg) or saline for 7 days, administered 1 hour before the session. Results Operant responding and methamphetamine intake were significantly higher in the extended-access protocol, and the drug intake showed an escalation in time. A single administration of liraglutide did not affect methamphetamine intake in either the short- or extended-access paradigms. Following repeated administration, liraglutide significantly decreased methamphetamine intake in the short-but not in the extended-access study. Conclusion The findings suggest that the GLP-1 receptor agonist liraglutide can reduce methamphetamine-taking behavior under conditions of low intake, whereas in the extended-access protocol, where drug intake escalates, the treatment shows no effect. Further research should better characterize its optimal dosing, duration of action, and brain penetration in rats.