Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils

There is a growing interest in the potential anxiolytic- and antidepressant-like effects of compounds that target neurokinin receptors. Since the structure and the pharmacology of the human neurokinin receptor resembles that of gerbils, rather than that of mice or rats, we decided to investigate the anxiolytic- and /or antidepressant-like effects of NK1 (SSR240600), NK2 (saredutant) and NK3 (osanetant) receptor antagonists in gerbils. It was found that saredutant (3-10 mg/kg, p.o.) and osanetant (3-10 mg/kg, p.o.) produced anxiolytic-like effects in the gerbil social interaction test. These effects were similar to those obtained with the V1b receptor antagonist SSR149415 (3-10 mg/kg, p.o.), diazepam (1 mg/kg, p.o.) and buspirone (10 mg/kg, p.o.). Fluoxetine and SSR240600 were devoid of effects in this test. In the tonic immobility test in gerbils, saredutant (5-10 mg/kg, i.p.) and osanetant (5-10 mg/kg, i.p.) produced similar effects to those observed with fluoxetine (7.5-15 mg/kg, i.p.), SSR149415 (10-30 mg/kg, p.o.) and buspirone (3 mg/kg, i.p.). Diazepam and SSR240600 were inactive in this paradigm. In conclusion, the present study indicates further that NK2 and NK3 receptor antagonists may have therapeutic potential in the clinical management of anxiety and depression.