Antidepressant-type effect of the NK3 tachykinin receptor agonist aminosenktide in mouse lines differing in endogenous opioid system activity

The influence of the tachykinin NK3 receptor agonist, aminosenktide on the immobility in the forced swimming test was studied in mouse lines selective ly bred for divergent magnitudes of stress-induced analgesia. The high anal gesia (HA) line is known to display enhanced, and the low analgesia (LA) li ne displays reduced activity of the opioid system. Aminosenktide at doses o f 125 mug/kg or 250 mug/kg intraperitoneally (IP) reduced, in naltrexone-re versible manner, the immobility more of opioid receptor-dense HA than of un selected mice, but was ineffective in the opioid receptor-deficient LA line . The effect of aminosenktide was quite similar to the antiimmobility actio n of desipramine (10 mg/kg IF), a prototypic antidepressant agent. None of the compounds increased animals' locomotion as found with an open field tes t; therefore their antiimmobility effect cannot be attributed to a change i n general motility. The results claim that aminosenktide causes an antidepr essant effect, and endogenous opioids are involved in this process. (C) 200 1 Elsevier Science Inc. All rights reserved.