Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 139, Issue 3, Pages 174-179Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2019.01.002
Keywords
KNT-127; D-cycloserine; Exposure therapy; Fear extinction; Contextual fear conditioning
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Funding
- Intramural Research Grant for Neurological and Psychiatric Disorders by the National Center of Neurology and Psychiatry, Japan [24-2, 27-1, 30-1]
- Japan Society for the Promotion of Science [17K07125]
- Grants-in-Aid for Scientific Research [17K07125] Funding Source: KAKEN
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Strategies to facilitate extinction of fear memory have attracted increasing attention for enhancing the effectiveness of exposure therapy for anxiety disorders. Previously, we demonstrated that systemic administration of a delta opioid receptor agonist, KNT-127, has clear anxiolytic-like effects in rats, without impairing memory. These observations led us to hypothesize that KNT-127 might be an appropriate therapeutic agent for anxiety disorders when combined with exposure therapy. In the present study, we demonstrate that KNT-127 (3 mg/kg) facilitates extinction learning of fear memory using the contextual fear conditioning test. As expected, a partial agonist at the glycine-binding site on the glutamatergic N-methyl-D-aspartate receptor, D-cycloserine (15 mg/kg), facilitated extinction learning of contextual fear in rats. In contrast, a benzodiazepine anxiolytic, diazepam (1 mg/kg), impaired the fear extinction learning. Interestingly, the facilitatory effect of KNT-127 on extinction learning was observed not only after a 10-min re-exposure, but also after a much shorter (2-min) re-exposure to the context, while D-cycloserine was ineffective at facilitating extinction when a short-duration exposure was given. Our findings may suggest that administration of a delta opioid receptor agonist might have therapeutic efficacy when combined with exposure therapy for treating a range of anxiety disorders. (c) 2019 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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