Drug addiction is a chronic and recurrent disease associated with learning and memory. Shaped by drug use and cues from the environment, drug memory serves a key role in drug‑seeking behaviour. Methamphetamine (MA), a globally abused drug, causes cognitive impairment, and endoplasmic reticulum (ER) stress is one of the mechanisms via which this occurs. In the current study, it was hypothesized that ER stress may serve a role in the disturbance of drug memory. The present study demonstrated that 5 mg/kg MA inhibited conditioned place preference behaviour via ER stress, which caused a disruption in long‑term potentiation in the hippocampus. When mice were pre‑treated with the ER stress inhibitors 4‑phenyl butyric acid or tauroursodeoxycholic acid, drug‑evoked synaptic plasticity was induced. Western blotting results indicated that treatment with 5 mg/kg MA enhanced the expression of cyclin‑dependent kinase‑5 and decreased the expression of Ca2+/calmodulin‑dependent protein kinase II α via ER stress. Collectively, the present results suggested that a large dose of MA inhibited drug‑evoked synaptic plasticity and disrupted drug memory by inducing ER stress.
Keywords: methamphetamine; endoplasmic reticulum stress; synaptic plasticity; addiction; drug memory.