curcumin and Morphine-Dependence

In recent years, the association between neuroinflammation and opioid dependence has attracted considerable attention. Curcumin, a component of the Curcuma longa, has been shown to act as a suppressor of glial cells and inflammatory cytokines. The main goal of this study was to explore the attenuating effects of curcumin on morphine dependence with a focus on neuroinflammation and μ-opioid receptors in the rat prefrontal cortex. To induce morphine dependence in male Wistar rats, morphine was administered i.p. once daily for 18 days in an escalating dose of 10, 20, and 40 mg/kg. Curcumin (2.5, 5, and 10 mg/kg, i.p.) was given from the days 10th to 18th. Immunofluorescence staining and ELISA methods were used to evaluate glial cells activity and inflammatory cytokines levels, respectively. Western blotting was used to evaluate the expression of μ-opioid receptors. The administration of curcumin (2.5, 5, and 10 mg/kg) for 9 days significantly attenuated the symptoms of morphine withdrawal syndrome. The prefrontal cortex concentration of TNF-α and IL-6 was also reduced by curcumin (2.5, 5, and 10 mg/kg) significantly. Furthermore, curcumin decreased the number of Iba1 and GFAP positive cells in morphine-dependent rats. Moreover, the expression of μ-opioid receptors was significantly reduced by curcumin (10 mg/kg). The results of this study demonstrate that curcumin attenuates morphine dependence in rats through an inhibitory effect on neuroinflammation and a decrease in the expression of μ-opioid receptors in the prefrontal cortex.

Topics: Animals; Curcumin; Cytokines; Male; Morphine; Morphine Dependence; Neuroglia; Neuroinflammatory Diseases; Rats; Rats, Wistar; Receptors, Opioid, mu; Substance Withdrawal Syndrome

Dendrosomal nanocurcumin (DNC) is fabricated from esterification of oleic acid and polyethylene glycol residues with curcumin. DNC has shown antioxidant, neuroprotective, and neurogenesis-enhancing effects. In addition, it can attenuate morphine tolerance. Morphine self-administration is associated with neurodegenerative changes of CA1 neurons in the adult hippocampus. The present study evaluated the effect of DNC pretreatment on morphine self-administration and hippocampal damage. Rats were pretreated with DNC (5 and 10 mg/kg, intraperitoneally) 30 min before a morphine self-administration paradigm performed in 2-h/sessions for 12 days under a FR-1 schedule. Pretreatment with both doses of DNC markedly suppressed morphine intake. Morphine self-administration resulted in a 71% reduction in the number of hippocampal CA1 neurons. DNC (5 mg/kg) pretreatment only marginally improved (by 22%) neuronal loss in this area. The data suggest that the effect of DNC on morphine self-administration is largely independent of the CA1 area. A functional restoration and regulation of reward circuit activity by DNC may reduce the motivation for morphine despite CA1 damage.

Topics: Animals; CA1 Region, Hippocampal; Catheters, Indwelling; Cell Count; Central Nervous System Agents; Curcumin; Disease Models, Animal; Male; Morphine; Morphine Dependence; Narcotics; Neurodegenerative Diseases; Neurons; Random Allocation; Rats, Wistar; Self Administration