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.
- Author:
Xian-Zhong JIANG
1
;
Yun-Feng LI
;
You-Zhi ZHANG
;
Hong-Xia CHEN
;
Ji LI
;
Nai-Ping WANG
Author Information
1. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
- Publication Type:Journal Article
- MeSH:
Adenylyl Cyclases;
metabolism;
Adrenergic alpha-Antagonists;
pharmacology;
Adrenergic beta-Antagonists;
pharmacology;
Agmatine;
administration & dosage;
pharmacology;
Animals;
Antidepressive Agents;
administration & dosage;
pharmacology;
Behavior, Animal;
drug effects;
Depression;
metabolism;
physiopathology;
Dose-Response Relationship, Drug;
Fenclonine;
pharmacology;
Idazoxan;
pharmacology;
Male;
Mice;
Pindolol;
pharmacology;
Random Allocation;
Rats;
Rats, Wistar;
Receptors, Biogenic Amine;
antagonists & inhibitors;
Serotonin 5-HT1 Receptor Antagonists;
Swimming;
Synapses;
enzymology;
Yohimbine;
pharmacology
- From:
Acta Pharmaceutica Sinica
2008;43(5):467-473
- CountryChina
- Language:Chinese
-
Abstract:
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, alpha2-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 radioimmunoassay. Single dose of agmatine (5-40 mg x 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 x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x 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 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
