effects of crocetin on histopathological changes of hippocampus induced by long term morphine injection

Opioid addiction is one of the major problems of the world. morphine is the main component of opium and directly affected the opioid receptors and has harmful effects by the production of free radicals and oxidative stress. chronic administration of morphine causes several adverse effects such as neurotoxicity, especially in the brain structures. crocetin (crt), an active ingredient in saffron, has been shown to have potent antioxidant and neuroprotective properties. the present study evaluated the protective effects of crocetin on the morphine_induced structural pathology of hippocampus. twenty-four male rats were randomly divided into 4 groups (n=6) and were treated intraperitoneally for 28 days with normal saline, morphine (20 mg/kg/day), and morphine (20 mg/kg/day) + crocetin (2.5 and 10 mg/kg/day). histological parameters were evaluated using hippocampal specimens. plasma levels of total antioxidant capacity (tac) and malondialdehyde (mda) were measured. the number of hippocampal neurons was also counted. morphine decreased tca, increased mda and reduced the number of neurons in the hippocampus. although morphine produced vacuolization and severe shrinkage of hippocampal neurons. blood tca and mda changes induced by morphine were improved with long-term i.p. injection of crocetin at doses of 10 mg/kg. crocetin prevented hippocampal neurons number loss and shrinkage in morphine group rats. we concluded that crocetin produced a neuroprotective effect through antioxidant activity.