Effects of potassium channel inhibitors in the forced swimming test: Possible involvement of l-arginine-nitric oxide-soluble guanylate cyclase pathway

• Published in: Behavioural brain research 2005-12, Vol.165 (2), p.204-209
• Main Authors: Kaster, Manuella P., Ferreira, Priscilla K., Santos, Adair R.S., Rodrigues, Ana L.S.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Anatomical correlates of behavior; Animals; Arginine - administration & dosage; Arginine - metabolism; Behavioral psychophysiology; Biological and medical sciences; Depression - drug therapy; Depression - enzymology; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors - administration & dosage; Escape Reaction - drug effects; Escape Reaction - physiology; Exploratory Behavior - drug effects; Female; Forced swimming test; Fundamental and applied biological sciences. Psychology; Guanylate Cyclase; Immobility Response, Tonic - drug effects; Immobility Response, Tonic - physiology; Injections, Intraventricular; K + channels; l-Arginine-nitric oxide pathway; Mice; Motor Activity - drug effects; Nitric Oxide - metabolism; Nitric Oxide Donors - administration & dosage; Piperazines - administration & dosage; Potassium Channel Blockers - administration & dosage; Potassium Channels - classification; Potassium Channels - drug effects; Potassium Channels - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Purines; Receptors, Cytoplasmic and Nuclear - metabolism; Signal Transduction - drug effects; Signal Transduction - physiology; Sildenafil Citrate; Soluble Guanylyl Cyclase; Statistics, Nonparametric; Stress, Psychological - metabolism; Sulfones; Swimming - physiology
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2005.06.031

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.