Reversal of Stress-Induced Social Interaction Deficits by Buprenorphine
| Autor: | Irwin Lucki, Edgardo Falcon, Olivier Berton, Shivon A. Robinson, Caroline A. Browne |
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| Rok vydání: | 2017 |
| Předmět: |
Male
medicine.medical_specialty ketamine medicine.drug_class Serotonin reuptake inhibitor Narcotic Antagonists Receptors Opioid mu κ-opioid receptor Regular Research Articles Social defeat Stress Disorders Post-Traumatic 03 medical and health sciences Mice 0302 clinical medicine Opioid receptor Internal medicine Fluoxetine medicine Animals Pharmacology (medical) Ketamine Social Behavior Pharmacology Behavior Animal business.industry Receptors Opioid kappa CERC-501 Brain PTSD social interaction buprenorphine 030227 psychiatry Mice Inbred C57BL Psychiatry and Mental health Disease Models Animal Endocrinology Opioid Anesthesia business Excitatory Amino Acid Antagonists 030217 neurology & neurosurgery Selective Serotonin Reuptake Inhibitors Stress Psychological medicine.drug Buprenorphine chronic social defeat stress |
| Zdroj: | International Journal of Neuropsychopharmacology |
| ISSN: | 1469-5111 |
| Popis: | Background Patients with post-traumatic stress disorder frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors, the only pharmaceutical class approved by the U.S. Food and Drug Administration for treating post-traumatic stress disorder. In this study, the sensitivity of social interaction deficits evoked by 10 days of chronic social defeat stress to prospective treatments for post-traumatic stress disorder was examined. Methods The effects of acute and repeated treatment with a low dose of buprenorphine (0.25 mg/kg/d) on social interaction deficits in male C57BL/6 mice by chronic social defeat stress were studied. Another cohort of mice was used to determine the effects of the selective serotonin reuptake inhibitor fluoxetine (10 mg/kg/d), the NMDA antagonist ketamine (10 mg/kg/d), and the selective kappa opioid receptor antagonist CERC-501 (1 mg/kg/d). Changes in mRNA expression of Oprm1 and Oprk1 were assessed in a separate cohort. Results Buprenorphine significantly reversed social interaction deficits produced by chronic social defeat stress following 7 days of administration, but not after acute injection. Treatment with fluoxetine for 7 days, but not 24 hours, also reinstated social interaction behavior in mice that were susceptible to chronic social defeat. In contrast, CERC-501 and ketamine failed to reverse social avoidance. Gene expression analysis found: (1) Oprm1 mRNA expression was reduced in the hippocampus and increased in the frontal cortex of susceptible mice and (2) Oprk1 mRNA expression was reduced in the amygdala and increased in the frontal cortex of susceptible mice compared to non-stressed controls and stress-resilient mice. Conclusions Short-term treatment with buprenorphine and fluoxetine normalized social interaction after chronic social defeat stress. In concert with the changes in opioid receptor expression produced by chronic social defeat stress, we speculate that buprenorphine’s efficacy in this model of post-traumatic stress disorder may be associated with the ability of this compound to engage multiple opioid receptors. |
| Databáze: | OpenAIRE |
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