The effect of the potassium channel activator, cromakalim, on antidepressant drugs in the forced swimming test in mice

Abstract

The forced swimming test (FST) is a widely used behavioural model to predict potential antidepressant (AD) action of compounds in humans. It has been previously shown that pretreatment with lithium, quinine and clonidine had additive effects on AD drugs in the FST, an effect proposed to be a result of potassium channel blockade. It is possible that pretreatment with potassium channel openers may induce opposite effects to those seen following pretreatment with potassium channel blockers in the FST. Pretreatment with cromakalim (CROM) (1 mg/kg, intraperitoneally [i.p.]) antagonized the anti-immobility effect of the mixed noradrenaline (NA)/5-hydroxytryptamine (5-HT) reuptake inhibitors imipramine and amitriptyline (P < 0.05). CROM administration (0.06 and 1 mg/kg, i.p.) also blocked the AD-like effects of the specific NA reuptake inhibitor, desipramine, and the selective serotonin reuptake inhibitor, paroxetine (P < 0.05 and P < 0.01, respectively). Pretreatment with CROM via gavage (1 mg/kg) antagonized the AD-like effects of imipramine, amitiptyline, desipramine and paroxetine. CROM treatment (via i.p. route or gavage) did not have any significant effect on the anti-immobility activity of the atypical AD mianserin at any of the doses employed. Another potassium channel opener, minoxidil (MINOX), which does not cross the blood-brain barrier, was also tested to eliminate the possibility that CROM may be acting via peripheral/local mechanisms. MINOX (32 mg/kg) failed to antagonize anti-immobility effects of any of the AD tested. In conclusion, the results of the present study suggest that CROM is only acting on drugs involved with neurotransmitter uptake inhibition.

Chronic Neonatal Diazoxide Therapy Is Not Associated With Adverse Effects

“…These results provide evidence for the involvement of K ATP channels in the induction of depressive-like phenotype. Our results correlate with previous studies that demonstrated this anti-immobility effect of various K ATP channel openers in the forced swim test (Galeotti et al , 1999; Redrobe et al , 1996). In addition, our data is the first to illustrate gender-specific involvement of KATP channel openers influence on immobility.…”

Pindolol does not act only on 5-HT 1A receptors in augmenting antidepressant activity in the mouse forced swimming test

“…Anti-immobility e¤ects of selective serotonin reuptake inhibitors were enhanced when these drugs were tested following prior administration of the 5-HT 3 receptor antagonist, ondansetron (Redrobe and Bourin 1997). Moreover, the anti-immobility e¤ects of such drugs were antagonized by prior administration of the potassium ion channel activator, cromakalim (Redrobe et al 1996b), results that further implicate a role for 5-HT 3 receptors in the activity of selected antidepressant drugs in the mouse forced swimming test.…”

Forced swimming test in mice: a review of antidepressant activity

“…Acute antidepressant treatment attenuates swim stress-induced corticosterone release in the rat (Baez and Volosin 1994). NK2-receptor antagonists, K + channel openers and K + channel blockers were considered for their antidepressant-like properties in the forced swim test (Guo et al 1996;Redrobe et al 1996;Slattery et al 2004). Nitric oxide synthase (NOS) or neurosteroids have been tested in the FST with mice to look for an antidepressant-like effect (Harkin et al 1999;Khisti et al 2000).…”