
Brain Research Bulletin, Год журнала: 2025, Номер unknown, С. 111364 - 111364
Опубликована: Апрель 1, 2025
The reasons for morphine dependence and withdrawal symptoms are oxidative stress dysfunction of cell mitochondria in the brain. Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), mitigates stress, while calcium channel blockers (nimodipine/diltiazem) prevent Ca²⁺-mediated mitochondrial dysfunction. In present study, effects simultaneous administration venlafaxine on syndrome role damage were assessed. this experimental analgesic effect venlafaxine, nimodipine, diltiazem was investigated using hot plate test to determine optimal doses drugs use subsequent experiments. To induce syndrome, male NMRI mice treated with 50mg/kg S.C. three consecutive days 5mg/kg fourth day. 2hours after last dose morphine, naloxone (5mg/kg) injected intraperitoneally, signs jumping standing evaluated 0.5hours. Venlafaxine (20mg/kg) alone or combination nimodipine (10mg/kg) (40mg/kg) administered half an hour before days. Brain slides stained examined under light microscope. isolated repeated centrifugation method investigate stress. dehydrogenase activity (MTT), membrane potential (MMP), ROS production rate, glutathione (GSH), malondialdehyde (MDA) contents brain measured. data expressed as mean±standard deviation, p-value less than 0.05 considered statistically significant. following injection increased compared control group (morphine followed by solvent naloxone) (P<0.01). Administration venlafaxine-nimodipine venlafaxine-diltiazem reduced these + decreased MTT GSH MDA, MMP, (P<0.01), alterations when (P<0.05). Coadministration could reduce its pathological damage. suggested mechanism event is preventing induced morphine.
Язык: Английский