Disulfiram Abrogates Morphine Tolerance-A Possible Role of µ-Opioid Receptor-Related G-Protein Activation in the Striatum.

摘要: One of the key strategies for effective pain management involves delaying analgesic tolerance. Early clinical reports indicate an extraordinary effectiveness off-label disulfiram-an agent designed alcohol use disorder-in potentiating opioid analgesia and abrogation Our study aimed to determine whether sustained µ-opioid signaling upon disulfiram exposure contributes these phenomena. Wistar rats were exposed acute chronic morphine cotreatment. Nociceptive thresholds assessed with mechanical Randal-Selitto thermal tail-flick tests. receptor activation in brain structures important processing was carried out [35S]GTPγS assay. The results suggest that (12.5-50 mg/kg i.g.) augmented antinociception diminished (25 mg/kg, tolerance a supraspinal, opioid-dependent manner. Disulfiram induced transient enhancement periaqueductal gray matter (PAG), rostral ventromedial medulla (RVM), hypothalamus, prefrontal cortex dorsal striatum at day 1 treatment. rescued nucleus accumbens caudate-putamen 14 days following this striatal receptors may contribute abolition concomitant treatment disulfiram.