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 microg/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 alpha2 adrenoceptors), atenolol (an antagonist of beta1 receptors), and raclopride (an antagonist of D2 receptors), but not prazosin (an antagonist of alpha1 adrenoceptors), ICI118551 (an antagonist of beta2 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, alpha2, beta1 and D2 receptors.
Iwai
Takashi
T
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Hayashi
Yohei
Y
Narita
Saori
S
Kasuya
Yuko
Y
Jin
Kazushi
K
Tsugane
Mamiko
M
Oka
Jun-Ichiro
J
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D015306:Biogenic Monoamines / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D053767:Glucagon-Like Peptide 2 / Q000627:therapeutic use*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009483:Neuropsychological Tests; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012149:Restraint, Physical; D015398:Signal Transduction / Q000187:drug effects; D013550:Swimming
D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D053767:Glucagon-Like Peptide 2; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin