The anxiolytic- and antidepressant-like effects of ATPM-ET, a novel [kappa] agonist and [mu] partial agonist, in mice

Rationale Opioid receptors are implicated in the regulation of motivation and emotion. However, animal studies show that activation of [kappa] opioid receptor produces contrasting mood-altering effects in models of anxiety-like and depressive-like behaviors, and consequently, the role of [kappa] receptor in mood control remains unsettled. The effect of [kappa]/[mu] opioid combination in emotion regulation was unexplored. Objectives The aim of the study was to investigate the effects of (-)-3-N-ethylaminothiazolo [5,4-b]-N-cyclopropylmethylmorphinan hydrochloride (ATPM-ET), a novel [kappa] agonist and [mu] partial agonist, in regulating emotional responses. Methods The emotional responses of ATPM-ET were detected in the elevated plus maze (EPM), open field test (OFT), forced swim test (FST), and tail suspension test (TST). Selective [kappa] antagonist nor-binaltorphimine (nor-BNI) and [mu] antagonist [beta]-funaltrexamine ([beta]-FNA) were applied to determine the type of receptor involved. The conditioned place aversion model was used to evaluate the effects on aversive emotion. Results In the EPM and OFT, ATPM-ET (1 and 2 mg/kg, s.c.) significantly increased the time spent in the open arm and in the central area, respectively. In the FST and TST, ATPM-ET (0.5 and 1 mg/kg, s.c.) significantly reduced the duration of immobility. These effects were prevented by nor-BNI (10 mg/kg, i.p., -24 h), but not by [beta]-FNA (10 and20 mg/kg, i.p., -24 h) pretreatment. At the dose of 2 mg/kg, ATPM-ET did not induce conditioned place aversion. Conclusions ATPM-ET, at doses from 0.5 to 2 mg/kg, produced anxiolytic- and antidepressant-like effects without inducing aversive emotion. These effects were more closely mediated by activation of [kappa] receptor than [mu] receptor.