ArticleNeurochemical research2025
TLRs/PI3K/AKT1B Signaling Pathway Is Involved in Modulation of Neuroinflammation in the Rat Hippocampus by Alpha-pinene in Morphine-dependent and Withdrawing Rats.
Article in Neurochemical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- The neuroimmune-glutamate hypothesis of addiction.Neuroscience and biobehavioral reviews · 2026Review
- Alpha-pinene modulates hippocampal MAPKs/c-Fos pathways during morphine dependence and withdrawal in rats.Psychopharmacology · 2026Article
- Immune signaling as a determinant of cellular identity and tissue function.Frontiers in immunology · 2026Review
- Zonisamide attenuates morphine tolerance in association with reduced spinal TLR4/p38 MAPK signaling.Frontiers in pharmacology · 2026Article
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Authors and funding
5 authors.
Funding
Abstract
Toll-like receptors (TLRs) in the brain significantly contribute to various central nervous system (CNS) disorders, including addiction. Morphine's interaction with TLR4 contributes to dependence and withdrawal. Alpha-pinene, a monoterpene with anti-inflammatory properties, has not been studied for its effects on TLR signaling in morphine dependence and withdrawal. This study investigated alpha-pinene's impact on hippocampal TLR pathways in morphine-dependent and withdrawing rats. Male Wistar rats were divided into two categories: dependence and withdrawal. The three dependence groups received saline + dimethyl sulfoxide 5% (DMSO), morphine (10 mg/kg) + DMSO, or morphine + alpha-pinene (20 mg/kg) for 10 days. The three withdrawal groups received the same saline or morphine treatments as the dependent groups for ten days. Following this, they went through a 30-day morphine washout phase with daily DMSO (the first and second groups) or alpha-pinene (the third group) administration. Rats in all groups were sacrificed either on day 10 (after repeated injections) or 30 days post-withdrawal. Hippocampal tissues were then dissected and analyzed via Western blot and ELISA to assess protein level changes. Results showed increased hippocampal expression of TLR2, TLR4, TLR10, and MyD88 following morphine dependence and withdrawal, while levels of PI3K, p-AKT1B, and IL-1Ra decreased. Alpha-pinene treatment, whether administered during the 10-days dependence induction period or the 30-days withdrawal period, partially restored these alterations in the TLR pathway. These findings suggest alpha-pinene modulates central immune responses by regulating TLR signaling. This highlights therapeutic potential of alpha-pinene for controlling neuroinflammation and subsequent morphine-related complications like tolerance, addiction, and withdrawal.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.