Effect of arachidonic acid cascade inhibitors on body temperature and cognitive functions in rats in the Morris water maze after acute cold injury.

Abstract

Objective: The aim of the study was to evaluate the effect of arachidonic acid cascade inhibitors on body temperature and cognitive functions of rats (spatial memory, learning ability) in the Morris water maze test (MWM) after acute cold injury (CI). Methods: Animals were trained to find an escape platform in the MWM for two consecutive days. On the third day, rats were treated with saline (10 ml/kg), diclofenac sodium (7 mg/kg), etoricoxib (5 mg/kg), darbufelone mesylate (20 mg/kg) or montelukast (1 mg/kg) intragastrically (i.g.), 30 minutes before CI modeling. Air hypothermia with an acute general cooling (AGC) model was used as a kind of CI. Animals were subjected to cooling for 2 hours at -18°C. Body temperature was measured before and after CI modeling. MWM experimental trials tests were carried out after cold exposure. Number of successful trials, escape latency, distance moved, velocity, meander, and behavioral patterns in individual quadrants were recorded. Results: In the control pathology group, a statistically significantly body temperature decrease was observed (p<0.05 compared to the initial value). All of the studied drugs reduced hypothermia severity, but only in the sodium diclofenac group this reduction reached a significant level in comparison with the untreated animals (p<0.01). A tendency to reduce the severity of hypothermia was observed in the group of animals treated by etoricoxib, darbufelone mesylate, and montelukast. In the control pathology group, the number of successful trials was significantly decreased (p<0.01), velocity (p<0.05), and escape latency (p<0.05) were increased compared with intact animals. Diclofenac sodium significantly reduced escape latency (p<0.05) and increased the number of successful trials in comparison with the control pathology group (p<0.01). Montelukast tended to improve, etoricoxib and darbufelone mesylate did not improve cognitive functions of rats with CI. Conclusions: The results experimentally substantiate the possibility of effective pharmacoprophylaxis of CI and its negative effects on cognitive functions while applying arachidonic acid cascade inhibitors, particularly the non-selective COX inhibitor diclofenac sodium.