It is widely accepted that mitogen-activated protein kinases (MAPKs) are involved in the neural alterations that occur due to prolonged exposure to addictive substances, such as morphine. Inhibit of MAPKs is a potential therapeutic advantage for patients in managing morphine addiction. Αlpha-pinene is a member of the monoterpene family that has exhibited several pharmacological properties, including anti-inflammatory effects. This study aimed to examine the effects of α-pinene treatment on the expression of MAPKs and levels of their phosphorylated form 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. Three 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 (group 1) or morphine treatments (groups 2 and 3). Then, throughout a 30-day withdrawal period, the saline-treated group and one of the groups treated with morphine received daily injections of DMSO, while the second group of morphine-treated animals received daily injections of α-pinene. The results revealed that expression of MAPKs, including p38, ERK1/2, and JNK did not significantly altered in the hippocampus after morphine dependence and following a 30-day withdrawal period. However, level of phosphorylated form of MAPKs significantly elevated in the rat hippocampus after both morphine dependence and withdrawal. Interestingly, treatment with α-pinene during either 10 days of the induction of dependence or 30 days of withdrawal period significantly restored phosphorylated form of MAPKs in the rat hippocampus by suppressing the c-Fos expression. It can be concluded that α-pinene could be a potential natural therapeutic for controlling overactivation of MAPKs due to morphine dependence and withdrawal by suppressing c-Fos expression. However, the involvement of other signaling cascades following α-pinene treatment cannot be excluded and clarifying this issue requires further experiments.
