EEffect of Chloroquine on Hyoscine-Induced Memory Impairment in Mice: Possible Involvement of Opioids and Nitric Oxide

Accumulating evidence suggests the potential use of chloroquine, an anti-malaria medication, as a neuroprotective agent. Moreover, several studies have reported that the endogenous opioids and nitric oxide (NO) may mediate the chloroquine’s effects. In the present study, effects of chloroquine on hyoscine-induced memory impairment were assessed. Furthermore, the possible involvements of opioids and NO were evaluated. Chloroquine was administered intraperitonially (i.p.) at doses of 0.1, 0.5, 1, 3, 10, and 20 mg/kg to hyoscine-treated (1mg/kg, i.p.) mice, and the spatial and fear memories were evaluated using Y-maze and passive-avoidance tasks, respectively. Also, to provide further evidence about chloroquine’s mechanism of action, the opioid receptors and the NO production were blocked using two nonselective antagonist’s naltrexone and L-NAME, respectively. Chloroquine at doses of  0.5, 10 and 20 mg/kg furtherly damaged the impaired memory of hyoscine-treated mice and at doses of 10 and 20 mg/kg impaired the memory of saline-treated mice in the passive-avoidance task. Additionally, chloroquine at doses of 0.5 and 1 mg/kg improved the spatial memory in hyoscine-treated mice in Y-maze test. In addition, naltrexone (3 mg/kg) reversed the neuroprotective effect of chloroquine (1 mg/kg) in hyoscine-treated mice in Y-maze task. It could be concluded that chloroquine at low doses may improve cognitive performances by involving the opioid receptors; as a result, blocking the opioid receptors may reverse chloroquine’s neuroprotective effect. Notably, chloroquine at high doses did not improve the memory and in combination with hyoscine, it caused even more damage to the long-term memory.