Naloxone-induced changes in tachykinin NK3 receptor modulation of experimental anxiety in mice

This study investigates the influence of naloxone, an opioid antagonist, upon the effects of drugs acting on tachykinin NK3 receptor in the elevated plus-maze test. Mice were intracerebroventricularly (i.c.v.) injected either with vehicle, 10 pmol of senktide, an NK3 agonist, or 100 pmol of [Trp7beta-Ala8]NKA(4-10) or SR142801, NK3 antagonists. Senktide alone significantly increased the frequency of entries and the time spent in open arms, an anxiolytic-like effect, whereas the NK3 antagonists alone showed no effect at the dose used. Naloxone alone did not alter the behavior of the animals on the plus-maze apparatus. Nevertheless, animals pretreated with naloxone (2 mg/kg, i.p.) showed an increase in senktide's anxiolytic-like effect and a similar profile of action for [Trp7beta-Ala8]NKA(4-10), but not for SR142801, which presented an anxiogenic-like effect. Altogether, these findings indicate a putative neurokinin-opioid relationship in the modulation of experimental anxiety in mice.