Increase in brain corticosterone concentration and recognition memory impairment following morphine withdrawal in mice.

Glucocorticoid hormones evidently affect memory. Morphine withdrawal causes a cognitive deficit and an increase in corticosterone secretion. In the present study brain corticosterone concentrations were determined after morphine withdrawal. Male mice were made dependent by increasing doses of morphine over 3 days. Blood and brain samples were collected following withdrawal induced by injection of naloxone (0.1 mg/kg) or spontaneously after 4 and 14 h. Brain corticosterone was extracted and measured by enzyme immunoassay. Short-term memory was determined in the novel object recognition task, using a 20 min interval between the learning trial and the test trial. In this memory trial, the difference in exploration between a previously seen object and a novel object is taken as an index of memory performance (recognition index, RI). RI in morphine dependent mice undergoing withdrawal was decreased compared to their control group. Brain corticosterone concentrations after naloxone withdrawal or 4 h after spontaneous withdrawal were respectively 22 and 34% greater than control values. Corticosterone concentration was normalized 14 h after the last dose of morphine. The results indicate that increase in brain corticosterone concentration may play an important role in short-term memory impairment following morphine withdrawal.