Additive effects of glyburide and antidepressants in the forced swimming test: evidence for the involvement of potassium channel blockade.
Evidence in the literature suggests that the modulatory effects of antidepressant drugs (ADS) on neuronal excitability, via the inhibition of K+ channels, may be the final common pathway of pharmacological action. Therefore, we tested the hypothesis that combining the ATP-sensitive K+ channel blocker glyburide with a variety of ADS would produce an additive effect and decrease the immobility time of mice in the forced swimming test (FST). Glyburide (GLY, IP, 30 and 50 mg/kg) and subactive doses of ADS were administered 45 and 30 min, respectively, prior to behavioral testing. Results showed that when combined with GLY, ADS whose main pharmacological effect is one of 5-HT uptake blockade (imipramine, amitriptyline, citalopram, paroxetine, fluoxetine, and fluvoxamine) were more effective in decreasing the amount of time mice were immobile, than when these drugs were administered alone. Some noradrenaline uptake inhibiting ADS (desipramine and viloxazine, but not maprotiline) were also significantly more effective in decreasing immobility time when combined with GLY than when administered alone. Pretreatment with GLY was found to have no effect on the dopamine uptake inhibitor bupropion, and out of the atypical ADS tested (trazodone, mianserine and iprindole), only coadministration with iprindole decreased the immobility time. Only the specific MAO-A inhibitor moclobemide was observed to have an antiimmobility effect when combined with GLY. Neither MAO-B specific (RO 16 6491) nor mixed MAO inhibitors (nialamide and pargyline) interacted with GLY to produce antiimmobility effects. These results corroborate and extend our previous report of the ADS enhancing effects of quinine in the same behavioral model, and suggest that the additive effects of quinine and GLY on ADS in FST are a result of K+ channel blockade.
Guo
W
W
Laboratoire de Pharmacologie et GIS Medicament, Faculté de Medecine, Université de Nantes, France.
Todd
K
K
Bourin
M
M
Hascoet
M
M
Kouadio
F
F
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005905:Glyburide / Q000494:pharmacology*; D007099:Imipramine / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D013550:Swimming
D000928:Antidepressive Agents; D007099:Imipramine; D005905:Glyburide