Effect of memantine hydrochloride on cisplatin-induced neurobehavioral toxicity in mice

Cisplatin is an anticancer agent widely used in the treatment of malignant tumors. One of the major adverse effects of cisplatin is its neurotoxicity. Memantine, an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, has been reported to have neuroprotective effects against neurological deficits. This study therefore investigated the possible protective role of memantine as an agent to minimize the neurobehavioral toxic side effects of cisplatin. Two different therapeutic doses of memantine (5 mg/kg) and (10 mg/kg) were orally administered for 30 days to 50 male BALB/c mice divided into 5 groups: G1: no treatment; G2: cisplatin treatment; G3: memantine treatment; G4: pretreatment of (5 mg/kg) memantine with cisplatin (4 mg/kg); G5: pretreatment of 10 mg/kg memantine with cisplatin (4 mg/kg). Weekly neurobehavioral investigations were conducted using the following battery of tests: open field activity, negative geotaxis, hole-board test, swimming test, and calculation of weight. At the end of the experimental period the mice were euthanized, and immunohistochemistry was then used to measure the expression scores of nicotinic acetylcholine receptors (nAChRs) in the muscles and brain. Results revealed that mice in G2 showed a significant decrease in the ability to perform neurobehavioral tasks. The mice in G5 exhibited a significantly improved ability on these tests, indicating a complete neurobehavioral protective effect, while the mice in G4 showed partial protection. The nAChRs score showed higher expression in the case of G2 in comparison with G3, G4, and G5. Weight loss was exhibited in G2, while in G3 and G1 these values were normal. A therapeutic dose of memantine 10 mg/kg yielded more protection than 5 mg/kg in the treatment of neuropathy; this highlights the importance of using memantine to decrease the main side effects of cisplatin.