Divergent effects of l-arginine-NO pathway modulators on diazepam and flunitrazepam responses in NOR task performance

Abstract

The goal of the study was an evaluation of the degree, in which nitric oxide (NO) is involved in the benzodiazepines (BZs)-induced recognition memory impairment in rats. The novel object recognition (NOR) test was used to examine recognition memory. The current research focused on the object memory impairing effects of diazepam (DZ; 0.5 and 1mg/kg, sc) and flunitrazepam (FNZ; 0.1 and 0.2mg/kg; sc) in 1-hour delay periods in rats. It was found that acute ip injection of l-arginine (l-arg; 250 and 500mg/kg; ip), 5min before DZ administration (0.5mg/kg, sc) prevented DZ-induced memory deficits. On the other hand, it was also proven that l-arg (125, 250 and 500mg/kg; ip) did not change the behaviour of rats in the NOR test, following a combined administration with FNZ at a threshold dose (0.05mg/kg; sc). It was also found that 7-nitroindazole (7-NI; 10, 20 and 40mg/kg; ip) induced amnesic effects in DZ in rats, submitted to the NOR test, following a combined administration of 7-NI with a threshold dose of DZ (0.25mg/kg; sc). However, following a combined administration of 7-NI (10, 20 and 40mg/kg; ip) with FNZ (0.1mg/kg; sc), it was observed that 7-NI inhibited the amnesic effects of FNZ on rats in the NOR test.Those findings led us to hypothesize that NO synthesis suppression may induce amnesic effects of DZ, while preventing FNZ memory impairment in rats, submitted to NOR tasks.