5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate cyclase activation in the mice brain are involved in the antidepressant-like action of agmatine
Jiang, X-Zhong.; Li, Y-Feng.; Zhang, Y-Zhi.; Chen, H-Xia.; Li, J.; Wang, N-Ping.
Yao Xue Xue Bao 43(5): 467-473
2008
ISSN/ISBN: 0513-4870 PMID: 18717332 Document Number: 620202
This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha(2)-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radio immunoassay. Single dose of agmatine (5 - 40 mg center dot kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg center dot kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg center dot kg(-1), ip), alpha(2)-adrenergic receptor antagonists yohimbine (5 - 10 mg center dot kg(-1), ip) or idazoxan (4 mg center dot kg(-1), ip), but not B-adrenergic receptor antagonist propranolol (5 - 20 mg center dot kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5 - 40 mg center dot kg(-1), ip). Agmatine (5 - 40 mg center dot kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg center dot kg(-1), ig) was also antagonized by pindolol (20 mg center dot kg(-1)) ip yohimbine (5 - 10 mg center dot kg(-1)) ip or idazoxan (4 mg center dot kg(-1), ip). Incubation of agmatine (0.1 +/- 6.4 mu mol center dot L-1) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6. 4 mu mol center dot L-1) was dose-dependently antagonized by pindolol (1 mu mol center dot L-1) or yohimbine (0.25 - 1 mu mol center dot L-1). Chronic treatment with agmatine (10 mg center dot kg(-1) ig, bid, 2 w) or fluoxetine (10 mg center dot kg(-1) ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH) p (1 - 100 mu mol center dot L-1) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha(2) receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.