Antidepressant-like effects of glucagon-like peptide-2 in mice occur via monoamine pathways

In this study, we investigated whether glucagon-like peptide-2 (GLP-2) had antidepressant-like effects in mice, and whether these activities were associated with monoamine systems in mice. Antidepressant-like effects were evaluated based on the immobility time in the forced-swim test. GLP-2 (1.5–6 μg/mouse, i.c.v.) significantly reduced the immobility time in a dose-dependent manner without affecting locomotor activity in the wheel running test and memory function in the step-down passive avoidance test. These effects were inhibited by pretreatment with metergoline (an antagonist of non-specific 5-HT receptors), parachlorophenylalanine (an inhibitor of 5-HT synthase), NAN-190 (an antagonist of 5-HT1A receptors), yohimbine hydrochloride (an antagonist of α2 adrenoceptors), atenolol (an antagonist of β1 receptors), and raclopride (an antagonist of D2 receptors), but not prazosin (an antagonist of α1 adrenoceptors), ICI118551 (an antagonist of β2 adrenoceptors), and SCH23394 (an antagonist of D1 receptors). These results suggest that GLP-2 exerts antidepressant-like effects in the forced-swim test in mice, which are associated with 5-HT1A, α2, β1 and D2 receptors.