Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice

Rationale Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered.Objectives To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice.Methods The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured.Results Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions.Conclusions Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.