Blocking effects of intra-hippocampal naltrexone microinjections on glucocorticoid-induced impairment of spatial memory retrieval in rats

Previous studies have indicated that stress levels of glucocorticoid hormones induce impairment of long-term memory retrieval. In a recent study, we have found that peripheral injections of naloxone blocked stress or glucocorticoid-induced deficit in memory retrieval, but the anatomical sites of such an interaction were not known. The present study examined whether the opioid receptors in the hippocampus interact with glucocorticoid effects on memory retrieval in a water maze (WM). Young rats carrying bilateral cannulae aimed at the hippocampus were trained in a WM task with six trials per day for six consecutive days. Retention of the spatial training was assessed 24 h after the last training session with a 60-s probe trial. Corticosterone (1 mg/kg) was injected 30 min before retention testing with or without prior bilateral intra-hippocampal injections of naltrexone (5, 10 or 20 μg/μl per site) as a classical opioid antagonist. The results show that corticosterone-induced impairment of memory retrieval was blocked by intra-hippocampal infusions of naltrexone in a dose-dependent manner. Moreover, even a higher dose of corticosterone (3 mg/kg) was ineffective in impairing memory retrieval in the animals that received 20 μg of naltrexone. These findings provide evidence for the view that glucocorticoids interact with the hippocampal opioid receptors in influencing long-term memory retrieval.