Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test.
The administration of agmatine elicits an antidepressant-like effect in the mouse forced swimming test by a mechanism dependent on the inhibition of the NMDA receptors and the L-arginine-nitric oxide (NO) pathway. Since it has been reported that the NO can activate different types of potassium (K(+)) channels in several tissues, the present study investigates the possibility of synergistic interactions between different types of K(+) channel inhibitors and agmatine in the forced swimming test. Treatment of mice by i.c.v. route with subeffective doses of tetraethylammonium (a non specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channels inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site), augmented the effect of agmatine (0.001 mg/kg, i.p.) in the forced swimming test. Furthermore, the administration of agmatine and the K(+) channel inhibitors, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time elicited by an active dose of agmatine (10 mg/kg, i.p.) in the forced swimming test was prevented by the pre-treatment of mice with the K(+) channel openers cromakalim (10 microg/site, i.c.v.) and minoxidil (10 microg/site, i.c.v.), without affecting locomotion. Together these data raise the possibility that the antidepressant-like effect of agmatine in the forced swimming test is related to its modulatory effects on neuronal excitability, via inhibition of K(+) channels.
Budni
Josiane
J
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis-SC, Brazil.
Gadotti
Vinícius M
VM
Kaster
Manuella P
MP
Santos
Adair R S
AR
Rodrigues
Ana Lúcia S
AL
D000376:Agmatine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001030:Apamin / Q000008:administration & dosage / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D018999:Charybdotoxin / Q000008:administration & dosage / Q000494:pharmacology; D019806:Cromakalim / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013550:Swimming / Q000502:physiology*; D019789:Tetraethylammonium / Q000008:administration & dosage / Q000494:pharmacology
D000928:Antidepressive Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D019806:Cromakalim; D018999:Charybdotoxin; D001030:Apamin; D009569:Nitric Oxide; D019789:Tetraethylammonium; D000376:Agmatine; D001120:Arginine; D005905:Glyburide