m-Trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 modulates the hippocampal neurotoxic adaptations and abolishes a depressive-like phenotype in a short-term morphine withdrawal in mice.

Abstract

The opioid withdrawal syndrome is defined as a complex phenomenon involving multiple cellular adaptations, which leads to the emergence of aversive physical and affective signs. The m-trifluoromethyl-diphenyl diselenide (m-CF3-PhSe)2 elicits an antidepressant-like effect by modulating the opioid system in different animal models of mood disorders. Notably, repeated exposure to (m-CF3-PhSe)2 developed neither tolerance nor withdrawal signs in mice. The aim of the present study was to investigate whether (m-CF3-PhSe)2 attenuates the physical signs and the depressive-like phenotype during morphine withdrawal through its neuroprotective effects on oxidative stress, the NMDA receptor and the proBDNF/mBDNF signaling in the hippocampus of mice. Adult Swiss mice received saline solution or escalating doses (20-100 mg/kg, sc) of morphine for six days. For the next three days, the animals were treated with canola oil, (m-CF3-PhSe)2 (5 and 10 mg/kg, ig) or methadone (5 mg/kg, sc) whereas morphine injections were discontinued. On day 9, physical withdrawal signs and depressive-like behavior were assessed 30 min after the last administration of (m-CF3-PhSe)2. Although short-term treatment with (m-CF3-PhSe)2 at both doses suppressed the aversive physical and affective signs in morphine withdrawn-mice, the highest dose of (m-CF3-PhSe)2 per se increased the teeth chattering manifestation. The intrinsic antioxidant property of (m-CF3-PhSe)2 modulated oxidative stress, it also restored the NMDA receptor levels in the hippocampus of morphine withdrawn-mice. Besides, (m-CF3-PhSe)2 downregulated the proBDNF/p-75NTR/JNK pro-apoptotic pathway without affecting the mBDNF/TrkB/ERK/CREB pro-survival signaling in the hippocampus of morphine withdrawn-mice. The results show that (m-CF3-PhSe)2 treatment modulated the hippocampal neurotoxic adaptations and abolished the depressive-like phenotype following morphine withdrawal in mice.

• Authors: Carolina C Martins, Suzan G Rosa, Ana M S Recchi, Cristina W Nogueira, Gilson Zeni
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 98 Pg. 109803 (03 02 2020) ISSN: 1878-4216 [Electronic] England
• PMID: 31689445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antidepressive Agents
• Narcotics
• Neuroprotective Agents
• Organosilicon Compounds
• m-trifluoromethyl-diphenyl diselenide
• Morphine

Topics

• Adaptation, Physiological
• Animals
• Antidepressive Agents (pharmacology)
• Behavior, Animal
• Depression (drug therapy)
• Hippocampus (drug effects, physiopathology)
• Mice
• Morphine
• Narcotics
• Neuroprotective Agents (pharmacology)
• Neurotoxicity Syndromes (physiopathology)
• Organosilicon Compounds (pharmacology)
• Oxidative Stress (drug effects)
• Phenotype
• Signal Transduction (drug effects)
• Substance Withdrawal Syndrome (drug therapy, physiopathology, psychology)