Relief of Morphine Withdrawal Symptoms by Japanese Sake Yeast Supplement (Saccharomyces Cerevisiae Sake) Through Adenosine A1 Receptor Activation in Mice Publisher



Bozorgi H¹ ; Rashidy Pour A² ; Moradikor N³ ; Darbanian H⁴ ; Tayyebi Sereshki A⁴ ; Seyedinia SA⁵ ; Tarahomi P⁵ ; Ganjeh MS⁵ ; Zarasvand AA⁶ ; Zamani P⁷
Source: Middle East Journal of Rehabilitation and Health Studies Published:2024

Abstract

Background: Morphine withdrawal syndrome is often treated with chemical drugs; however, these drugs can have concerning side effects. Some natural substances might offer safer alternatives for managing withdrawal symptoms. The neuroprotective activity of the adenosine A1 receptor (A1 R) in the central nervous system (CNS) has been mentioned before. As a novel natural agent, Japanese sake yeast is enriched with adenosine analogs. Objectives: As the first report, the present study was designed to evaluate the effects of the Japanese sake yeast supplement against the excitatory signs of morphine withdrawal syndrome in mice. Methods: Mice were treated orally (gavage) with sake yeast at doses of 100, 200, and 300 mg kg-1 once daily for a week. Furthermore, during the last 3 days of receiving sake yeast, the animals were made physically dependent on morphine by being given twice-daily subcutaneous injections of increasing doses of morphine (30-90 mg/kg) for 3 consecutive days. The withdrawal syndrome was induced in animals through the intraperitoneal (i.p.) administration of naloxone (3 mg kg-1) or was elicited spontaneously. After the examination of withdrawal signs, the animals were decapitated, and their brains were prepared for histopathology. Results: Sake yeast alleviated the intensity of ptosis, piloerection, diarrhea, irritability, and tremor during the two withdrawal syndrome protocols (P < 0.05) and diminished the number of jumping in naloxone-induced withdrawal syndrome (P < 0.01). The withdrawal symptom-lowering effect of sake yeast was reversed by the i.p. injection of an A1R-selective antagonist, 8-cyclopentyltheophylline (10 mg kg-1), and maintained following the i.p. injection of ZM241385 (15 mg kg-1), a selective adenosine A2AR antagonist. Furthermore, histopathological findings demonstrated that sake yeast at doses of 200 and 300 mg kg-1 inhibited the CA1 hippocampal neuronal damage induced by withdrawal syndrome (P < 0.05). Conclusions: Sake yeast suppresses the morphine withdrawal syndrome via the activation of A1 R. © 2023, Author(s).