Neuroprotective effects of cinnamaldehyde and naltrexone on morphine-induced hippocampal neurotoxicity: Behavioral,...

Chronic consumption of opiates such as morphine can exert serious adverse effects such as cognitive disturbances. Cinnamaldehyde has a potent neuroprotective property. The current study was targeted to explore the effect of cinnamaldehyde on morphine-induced behavioral and hippocampal biochemistry, histopathology and ultrastructure outcomes and molecular changes. Thirty rats were divided into five groups of six rats in each for receiving normal saline + normal saline, normal saline + morphine 40 mg/kg, cinnamaldehyde 10 mg/kg + morphine 40 mg/kg, cinnamaldehyde 20 mg/kg + morphine 40 mg/kg and naltrexone (an opioid receptor antagonist) 5 mg/kg + morphine 40 mg/kg. Another 24 rats were divided into four groups of six for treating with the above-mentioned treatments in the absence of morphine. Weekly body weight, behavioral tests and hippocampal tissue biochemical, histopathological, ultrastructural alterations were determined. Morphine-induced body weight loss and cognitive deficits, as measured with the Morris water maze (MWM) and elevated plus maze-transfer latency (EPM-TL) tests, were improved by cinnamaldehyde and naltrexone. Hippocampal malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant (TAC), tumor necrosis factor-α (TNF-α), caspase-3, and acetylcholinesterase (AChE) content alterations were restored by cinnamaldehyde and naltrexone. Neuronal shrinkage, vacuolation and loss and mitochondrial vacuolation and myelin sheath lamellar spacing in the hippocampus were improved. No significant differences were observed in normal saline, cinnamaldehyde and naltrexone treatments in the absence of morphine. These results indicated that cinnamaldehyde and naltrexone exert neuroprotective effects against morphine-induced cognitive deficits through antioxidant, anti-inflammatory, anti-apoptotic and anti-AChE mechanisms in the hippocampus.