Alpha-pinene attenuates neuroinflammatory responses in the rat hippocampus and improves spatial working memory...

Chronic morphine exposure leads to changes in neural function, with neuroinflammation playing a key role in these disruptions. The monoterpene compound α-pinene has been shown to possess properties that counteract inflammation. This study focused on assessing how α-pinene reduces inflammation and improves spatial working memory deficits resulting from frequent morphine exposure and following the drug washout. First, spatial working memory was assessed by using the Y-maze test in male Wistar rats. Then, levels of proinflammatory cytokines and expression of their receptors in the rat hippocampus were analyzed using ELISA and western blot methods. The findings demonstrated that 10 days of morphine administration weakened spatial memory, an effect that was partially alleviated by concurrent α-pinene treatment during morphine exposure. Although 30 days washout period modestly improved the memory deficit, α-pinene administration during withdrawal further augmented the recovery of memory function. Molecular analyses revealed substantial rises in hippocampal levels of TNFα, IL-1β, and IL-6, alongside expression of their associated receptors (TNFR, IL1R, and IL6R) as well as NF-κB following the morphine exposure and 30 days of the washout period. Conversely, the hippocampal concentrations of IL-10 as an inhibitory factor in inflammation were reduced. Notably, α-pinene treatment, whether administered during dependence induction or throughout withdrawal, markedly normalized proinflammatory cytokine levels and receptor expression in the hippocampus by affecting total NF-κB levels, but not its phosphorylation. It can be concluded that α-pinene may serve as a potential natural therapy for the management of neuroinflammation and recovering spatial memory following chronic morphine exposure and withdrawal.