The inhibition of different types of potassium channels underlies the antidepressant-like effect of adenosine in the mouse forced swimming test.
It was previously shown that the acute administration of adenosine elicits an antidepressant-like effect in the mouse forced swimming test (FST) by a mechanism dependent on the inhibition of the L-arginine-nitric oxide (NO)-guanylate cyclase pathway. Taken into account that the stimulation of this pathway is associated with the activation of K(+) channels, this study investigated the involvement of different types of K(+) channels in the effect of adenosine in the FST. Intracerebroventricular treatment of mice with tetraethylammonium (TEA, a non-specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channel 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) was able to potentiate the action of subeffective doses of adenosine (1 mg/kg, i.p.) and fluoxetine (a serotonin reuptake inhibitor, 10 mg/kg, i.p.). Furthermore, the administration of adenosine or fluoxetine and the K(+) channel inhibitors, alone or in combination, did not affect the ambulatory behavior. Moreover, the reduction in the immobility time elicited by active doses of adenosine (10 mg/kg, i.p.) or fluoxetine (32 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with cromakalim (a K(+) channel opener, 10 microg/site, i.c.v.), without affecting the locomotion in an open-field. Together these results indicate that the modulatory effects of adenosine and fluoxetine on neuronal excitability, via inhibition of K(+) channels, may represent the final pathway of their antidepressant-like effects in the FST.
Kaster
Manuella P
MP
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário-Trindade-88040-900, Florianópolis-SC, Brazil.
Budni
Josiane
J
Binfaré
Ricardo W
RW
Santos
Adair R S
AR
Rodrigues
Ana Lúcia S
AL
D000241:Adenosine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D019806:Cromakalim / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D046353:Immobility Response, Tonic / Q000187:drug effects; D007276:Injections, Intraventricular / Q000379:methods; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009433:Neural Inhibition / Q000187:drug effects*; D010276:Parasympatholytics / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D013550:Swimming / Q000523:psychology; D019789:Tetraethylammonium / Q000494:pharmacology
D000928:Antidepressive Agents; D010276:Parasympatholytics; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019806:Cromakalim; D019789:Tetraethylammonium; D000241:Adenosine