Effects of potassium channel inhibitors in the forced swimming test: possible involvement of L-arginine-nitric oxide-soluble guanylate cyclase pathway.
The effects of inhibitors of different subtypes of potassium (K+) channels were investigated in the mouse forced swimming test (FST). The treatment of animals with tetraethylammonium (TEA, a non-specific inhibitor of potassium channels, 0.25-2.5 ng/site, intracerebroventricular, i.c.v.), glibenclamide (an ATP-sensitive potassium channels (K(ATP) inhibitor, 0.05-5 ng/site, i.c.v.), apamine (a small conductance calcium-activated potassium channels inhibitor (SKCa), 0.1-1 ng/site, i.c.v.), charybdotoxin (a large- (big, BK) and intermediate- (IK) conductance calcium-activated potassium channels inhibitor, 2.5-25 ng/site, i.c.v.) produced an anti-depressant-like effect in the FST. At the highest effective doses, none of the drugs affected the locomotor activity in an open-field. Besides that, the pre-treatment of animals with l-arginine (a nitric oxide (NO) precursor, 750 mg/kg, intraperitoneal, i.p.) or sildenafil (a specific phosphodiesterase type 5 (PDE5) inhibitor, 5 mg/kg, i.p.) prevented the anti-depressant-like effect of all K+ channel inhibitors. The present results demonstrate that the decrease in the immobility time in the FST elicited by the inhibition of several subtypes of K+ channels is also dependent on the inhibition of NO-cGMP synthesis.
Kaster
Manuella P
MP
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88040-900, Florianópolis-SC, Brazil.
Ferreira
Priscilla K
PK
Santos
Adair R S
AR
Rodrigues
Ana L S
AL
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000378:metabolism; D003863:Depression / Q000188:drug therapy / Q000201:enzymology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006162:Guanylate Cyclase; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D026902:Potassium Channel Blockers / Q000008:administration & dosage*; D015221:Potassium Channels / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D011687:Purines; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000068677:Sildenafil Citrate; D000071756:Soluble Guanylyl Cyclase; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000378:metabolism; D013450:Sulfones; D013550:Swimming / Q000502:physiology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010879:Piperazines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011687:Purines; D018160:Receptors, Cytoplasmic and Nuclear; D013450:Sulfones; D009569:Nitric Oxide; D001120:Arginine; D000068677:Sildenafil Citrate; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase