Administration of a delta opioid receptor agonist KNT-127 to the basolateral amygdala has robust anxiolytic-like effects in rats

Rationale We previously reported that systemic administration of a selective delta opioid receptor (DOP) agonist, KNT-127, produced potent anxiolytic-like effects in rats. Interestingly, DOPs are highly distributed in the basolateral region of the amygdala (BLA). Objectives In this study, we investigated the effect of intra-BLA administration of KNT-127 on anxiety-like behaviors in rats. Methods and Results In the elevated plus maze test, bilateral injection of KNT-127 into the BLA significantly and dose-dependently increased time spent in the open arms. The magnitude of KNT-127 (0.08 mu g/0.2 mu l)-induced anxiolytic-like effects was similar to muscimol (0.1 mu g/0.2 mu l), which is a selective agonist for the gamma amino butyric acid type A receptors. Further, anxiolytic-like effects of KNT-127 were abolished by pretreatment with naltrindole, a selective DOP antagonist, suggesting that KNT-127-induced anxiolytic-like effects are mediated by DOPs. These anxiolytic-like effects were confirmed using another innate anxiety model, the open field test. Interestingly, intra-BLA administration of KNT-127 also induced anxiolytic-like effects in the contextual fear conditioning test. Moreover, these effects were also abolished by naltrindole pretreatment. Finally, we demonstrated that intra-BLA administration of KNT-127 facilitates extinction learning of contextual fear in conditioned rats. Conclusions Altogether, our findings clearly demonstrate that intra-BLA administration of KNT-127 in rats has robust anxiolytic-like effects not only in innate anxiety-like behavioral tests but also in the contextual fear conditioning test.