Selective imidazoline I2 ligands do not show antidepressant-like activity in the forced swim test in mice.

Clonidine is an adrenergic agonist with high affinity for alpha2 adrenoceptors that also has affinity for imidazoline receptors. Clonidine has previously been shown to reduce immobility in the forced swim test (FST) in mice. In the present study, this effect was blocked by idazoxan (0.06 mg/kg s.c.) and by yohimbine (1.0 mg/kg s.c.) suggesting that clonidine's effects in this test are mediated via its action at alpha2 sites. Imidazoline I2 site ligands have been shown to inhibit monoamine oxidase and thus may also have antidepressant activity. Three compounds with selective affinity for I2 receptors (BU224, BU239, BDF 8082) were also tested in the FST. These compounds showed no activity either alone or in combination with a subthreshold dose of imipramine in the FST. These results suggest that I2 receptor ligands do not show antidepressant-like activity in the FST in mice. Furthermore the activity of the mixed alpha2/I1 agonist clonidine is most likely to be due to its action at alpha2 sites.

Role of 5-HT(1A) and 5-HT(1B) receptors in the mediation of behavior in the forced swim test in mice.

The purpose of this study was to further examine the effect of activation of 5-HT(1A) and 5-HT(1B) receptors in the forced swim test in mice and to determine if activation of these receptors played a role in the mediation of the effects of the tricyclic antidepressant imipramine. The 5-HT(1A) agonist 8-OH-DPAT decreased immobility in the forced swim test in mice as previously described. Both the selective 5-HT(1B) agonist anpirtoline (1.25-5 mg/kg) and mixed 5-HT(1A/B) agonist RU24969 (0.6-2.5 mg/kg) significantly increased time spent swimming in the FST.