Abstract
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 μg/0.2 μl)-induced anxiolytic-like effects was similar to muscimol (0.1 μg/0.2 μl), 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.
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Acknowledgments
We thank Rachel James, Ph.D., from Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript.
Funding
This research was financially supported by an Intramural Research Grant (24-2, 27-1, 30-1) for Neurological and Psychiatric Disorders provided by the National Center of Neurology and Psychiatry, Japan (NCNP). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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The studies were conducted in accordance with protocols approved by the Institutional Animal Care and Use Committee of the Japanese National Center of Neurology and Psychiatry (Approval No. 2010001).
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The authors declare that they have no conflict of interest.
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Sugiyama, A., Yamada, M., Saitoh, A. et al. Administration of a delta opioid receptor agonist KNT-127 to the basolateral amygdala has robust anxiolytic-like effects in rats. Psychopharmacology 235, 2947–2955 (2018). https://doi.org/10.1007/s00213-018-4984-7
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DOI: https://doi.org/10.1007/s00213-018-4984-7