The Effect of Co-Administration of Nitric Oxide and Morphine in CA3 of Hippocampus on Learning and Spatial Memory in Normal and Morphine Dependent Male Rats

摘要

Induction of synaptic plasticity in hippocampus is the main mechanism of learning and memory and various agents can influence theme. Opioids resulted to tolerance, dependency and cognitive deficits But the effect of morphine dependency on learning and memory is still controversial. In this study the effect of co-administration of nitric oxide(NO) and morphine in CA3 of hippocampus on learning and spatial memory in normal and morphine dependent male rats was investigated. Male rats were anaesthetized and cannula implanted bilaterally in CA3 of hippocampus via stereotax. After recovery period, rats were used in 2 normal and morphine dependent groups, that in last group morphine dependency was induced by subcutaneous injection of morphine for 5 days. Then each group subdivided to 6 subgroups that received 1μl of drugs for 5 testing days. Drugs were saline, L-Arginine(0.3M and 3 μl/rat), L-NAME(0.3M), morphine(10mg) individually and L-Arginine with morphine or L-NAME with morphine. Then animals were trained in Morris water maze to evaluate learning and spatial memory. Results showed that in normal rats, L-Arginine improved learning and spatial memory and L-NAME or morphine impaired theme. In morphine dependent rats, L-NAME decreased learning but morphine did not affect learning and spatial memory. Co-administration of L-NAME with morphine in normal rats decreased learning more than morphine individually and in morphine dependent rats, co-administration of L-Arginine with morphine not only improved the effect of morphine on learning but also promote the effect of L-Arginine on learning.