Agmatine produces antidepressant-like effects in two models of depression in mice.
Agmatine produces an antidepressant-like effect when assessed in the forced swimming test (FST) and in the tail suspension test (TST) in mice (dose range 0.01-50 mg/kg, i.p.), without accompanying changes in ambulation in an open-field. I.c.v. injection of agmatine (1-100 nmol/site) also reduced the immobility time in the FST. Agmatine significantly enhanced the anti-immobility effect of imipramine, but did not affect that of MK-801. The anti-immobility effect of agmatine assessed in the FST was not affected by pre-treatment with prazosin. In contrast, agmatine's antidepressant-like effect was completely prevented by pre-treatment of animals with yohimbine, GMP or L-arginine. Taken together these data demonstrate that agmatine elicited a significant antidepressant-like effect through a mechanism that seems to involve an interaction with NMDA receptors, the L-arginine-nitric oxide pathway and alpha2-adrenoceptors.
Zomkowski
Andrea D E
AD
Departamento de Bioquímica and Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, 88040-900, Florianópolis, Brazil.
Hammes
Luciana
L
Lin
Jaime
J
Calixto
João Batista
JB
Santos
Adair Roberto S
AR
Rodrigues
Ana Lúcia S
AL
D000376:Agmatine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007099:Imipramine / Q000627:therapeutic use; D008297:Male; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D016194:Receptors, N-Methyl-D-Aspartate; D000376:Agmatine; D019001:Nitric Oxide Synthase; D007099:Imipramine