Neuroinflammation is involved in the neural alterations that occur due to prolonged exposure to addictive substances, such as morphine. Research shows that controlling inflammatory responses is a potential therapeutic advantage for patients in managing addiction and restoring analgesic effect of morphine. α-pinene is a member of the monoterpene family that has exhibited several pharmacological properties, including anti-inflammatory properties. The aim of this study was to examine the effects of α-pinene treatment on the expression of proinflammatory cytokines and their receptors in the rat hippocampus after morphine dependence and withdrawal. Six groups of male Wistar rats were used in two categories, including dependent and withdrawal categories. Experimental groups of the first category received 10 days of either saline + DMSO, morphine (10 mg/kg) + DMSO, or morphine + α-pinene (20 mg/kg). Three experimental groups of the second category received 10 days of either saline (one group) or morphine treatments (two groups). Then, throughout a 30-day withdrawal period, the saline-treated group and one of the groups treated with morphine were administered daily injections of DMSO, while the second group of morphine-treated animals received daily injections of α-pinene. The results revealed that morphine dependence and withdrawal are associated with significant increases in inflammatory cytokines, including TNFα, IL-1β, IL-6, and their respective receptors, including TNFR, IL1R, and IL6R as well as NF-κB in the rat hippocampus. The hippocampal levels of anti-inflammatory cytokine IL-10 were decreased after morphine dependence and withdrawal. Interestingly, treatment with α-pinene either over 10 days of the induction of dependence or during 30 days of withdrawal period significantly restored proinflammatory cytokine levels, expression of their receptors, and IL10 levels in the rat hippocampus by suppressing NF-κB. It can be concluded that α-pinene could be a potential natural therapeutic for controlling inflammation due to morphine dependence and withdrawal by suppressing NF-κB, restoring positive effects of morphine and postponing its negative consequences. However, activation or suppression of other signaling cascades following α-pinene treatment cannot be excluded and requires further experiments.
