Effects of Agents Influencing Serotonergic and Cannabinoid Systems on Memory in the Avoidance Test in Mice

摘要

Adult male albino mice in a shuttle box system were used for examination of learning for avoidance behavior and its deactivation. We measured the step-through latency in the acquisition of the task (STLa) before injections of the drugs tested (fluoxetine and URB597, a serotonin reuptake inhibitor, SSRI, and an agent preventing decomposition of endocannabinoids, respectively) and the respective latency 24 h after injections of these agents (STLr); total time spent in the dark compartment (TDC) was also measured in these situations. In mice that received fluoxetine (5, 10, and 20 mg/kg), the STLr were longer than those in the control, and the difference was significant at 10 mg/kg. Injections of URB597 decreased the STLr, and at medium and high doses (0.3 and 1.0 mg/kg) significant differences were observed. All doses of fluoxetine led to significant decreases in the TDC values, while injections of URB597 increased this index (at 0.3 and 1.0 mg/kg, the shifts were significant). Combined injections of fluoxetine and URB597 (5 + 0.1, 10 + 0.3, and 20 + 1.0 mg/kg) increased the STLr values and decreased TDC values to levels comparable with those at isolated injections of fluoxetine in the respective doses. Thus, fluoxetine improves memory, while URB597 impaired it; fluoxetine is capable of nullifying th e negative effects of URB597.