NITRIC OXIDE WITHIN THE RAT HIPPOCAMPAL CA1 AREA MAY PLAY A ROLE IN MORPHINE TOLERANCE

Abstract

Hippocampus as part of the limbic system plays an important role in abused drugs-induced memory. The role of glutamate receptor within the hippocampal CA1 area in morphine-induced memory has also been postulated. Previous studies indicated that glutamate receptors exert their effects in part through the release of nitric oxide (NO). In the present study, the effects of intra-CA1 area injections of L-arginine (0.3, 1, and 3 ?g/rat), the NO precursor and L-NAME (0.3, 1, and 3 ?g/rat), the NOS inhibitor on the morphine tolerance in Wistar rats (250-300 g) were investigated. Male rats (n = 8/group) were anesthetized and bilateral cannulation in nucleus accumbens (21-gauge, AP = -3.8mm, L = ±1.8, V = 2.5 mm) was performed. Five days after cannulation, animals were trained in an Un-Biased conditioned place preference apparatus for five consecutive days. The NOergic drugs were injected in two ways: first; the animals were trained with morphine and were received L-arginine or L-NAME at 5th day of experiments just before the test. Second group received L-arginine or L-NAME before morphine injection. At the 5th day of the experiments, each animal was placed in the apparatus and its behavior was recorded for 10 min. The results showed that pretreatment of the animals with L-arginine inhibit morphine tolerance. Pretreatment of the animals with L-NAME did not show any effect on morphine tolerance. In conclusion, present experiments showed that morphine tolerance is in part dependent to NO system activation within the hippocampus CA1 area and the role of this neuromodulator in morphine tolerance must be considered in further treatments of morphine addicts.