Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists are increasingly recognised for their effects on addiction. In this study I examined the effect of the GLP-1R agonist liraglutide on reward-related brain activity and motivated behaviour.
Activity was recorded from the lateral septum (LS), in rats (n = 3), as animals received first saline and then 0.06 mg/kg Liraglutide. I then assessed the behavioural effects of liraglutide in rats (n = 12) using the progressive ratio (PR) task, in which rats must progressively increase responding for reward. Each subject completed two sessions (PR1 and PR2) following injections of either saline, 0.03 mg/kg, or 0.06 mg/kg liraglutide. “Control” (n = 6) received saline across both sessions, and “Drug” (n = 6) received 0.03 mg/kg during PR1 and 0.06 mg/kg during PR2.
The completed ratio during PR2 (mean = 48.33) was significantly reduced compared to PR1 (mean = 87.17) (SEM = 13.91, p = 0.0187), as was the total number of lever presses (PR1 mean = 128.7, PR2 mean = 50.50) (SEM = 13.99, p = 0.0052). To assess the effects of GLP-1R agonism on the ability to inhibit behaviour, rats were trained on a 15-second Differential Reinforcement of Low Rates (DRL-15) task. In this task, animals must wait 15s before responding is rewarded. Premature responses reset the timer. Chronic liraglutide (0.06 mg/kg) (mean = 15.27s) significantly increased the time between responses compared to saline (mean = 14.05s), (p = 0.0473). During this experiment, all animals experienced all drug levels in the order of saline: 0.03 mg/kg-0.06 mg/kg. Across all experiments, injections were administered 1 hr prior to testing. Behavioural data were analysed using 2×2 repeated-measures ANOVA.
These findings support the theory that GLP-1 agonists modulate reward representation and motivation for rewards. With the increasing use of GLP-1 agonists for weight loss, clarifying their effects on motivation is of increasing significance.