ArticleIranian journal of basic medical sciences2026
Linalool restores post-morphine hippocampal-striatal PI3K/Akt and CREB/ΔFosB mRNA expression and LFP power in adult male rats.
Article in Iranian journal of basic medical sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objectives: Opioid use disorder (OUD) is a chronic, relapsing condition characterized by compulsive drug seeking and profound abstinence-related disturbances. Opioid receptors are distributed across reward-related regions, including the ventral tegmental area (VTA), the ventral striatum (VS), and the hippocampus. Key mediators-PI3K-Akt in the hippocampus and CREB/ΔFosB in the striatum-modulate opioid addiction along the hippocampal-VS axis. Materials and Methods: Rats underwent conditioned place preference (CPP) with three phases: pre-conditioning, conditioning, and post-conditioning. During conditioning, animals received morphine (10 mg/kg, IP) for three days, with or without linalool (50 mg/kg, IP, 30 min prior to morphine). This three-day protocol models reward learning rather than chronic dependence. Groups: saline, morphine, and morphine+linalool. Behavioral tests assessed CPP score, passive avoidance memory, anxiety- and depression-like behaviors, and locomotion. Molecular analyses measured PI3K and Akt mRNA expression (real-time PCR) in the hippocampus and CREB/ΔFosB in the VS. Local field potentials (LFPs) were recorded directly from the hippocampal CA1 and the nucleus accumbens (NAc, part of the VS) via implanted electrodes. Results: Linalool significantly attenuated morphine-induced CPP, improved passive avoidance memory, and reduced anxiety/depressive-like behaviors. Linalool decreased morphine-induced up-regulation of CREB/ΔFosB in VS and PI3K/Akt mRNA in the hippocampus. LFP power in CA1 and NAc was reduced by morphine and restored by linalool. Conclusion: Linalool attenuates morphine-induced reward, memory deficits, and affective disturbances, which are key features of opioid abstinence-induced behavioral disturbances, and normalizes molecular and electrophysiological alterations in the hippocampal-striatal circuit. Although direct causality is not established, linalool is a promising natural compound for managing opioid-associated behavioral disturbances.
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