ObjectivePhysical activity increases brain activity through mechanisms, not yet known. Several research suggest that exercise could have modified neurotransmission of the brain. In addition, recent researches show that glutamate play important role in the morphine dependent rats. On the basis of these results, we studied the effect of treadmill running on variation of glutamate concentration from hypocampal dentate gyrus in the intact and morphine dependent rats.Materials and MethodsTwenty-eight healthy male rats, weighting about 250 g, were assigned to one of four groups as follows: control, morphine, physical activity, morphine with physical activity. Intraperitoneal injection of dissolved morphine with increasing doses of 10 mg/kg, 20 mg/kg and 40 mg/kg, for first, second and third three days, respectively, were applied to make rats morphine dependence. Compulsive running on rat treadmill were performed in a ten-day period (2hr a day, at a speed of 12m/min and an incline of 15 degrees) for the two groups of physical activity and morphine with physical activity. Microdialysis was perfoffi1edseparately and individually for each group (one rat per day). At microdialysis stage, rat was correctly weighted and the anesthetic agent of chloral hydrate 10% at a dose of 450 mg/kg was received through intraperitoneal injection. Then the anesthetized rat was placed in rat specified stereotaxis apparatus, the skull was opened and cleaned, so that the Bregma and Lambda points were identified, and the dimensions of the hypocampal dentate gyrus (DG) were obtained from the atlas of rats brain stereotaxis and hole was made by dentists drill in the location and the micodialysis probe was placed in the measured location in a very accurate manner. Then a CSF (NaCl, KCI, MgCl2, Na2HPO4, NaH2PO4, CaCl2 and Glucose) was entered into probe by microinjection pump with speed of 2 ml/min and the output of the probe was collected in numbered vials. The first hour of output was discharged and afterwards the output of the probe was collected every 20 minutes and immediately kept at -70°C. Finally, glutamate concentration was measured by HPLC method using florescence detector and the results were statistically analyzed.ResultsThe results indicated that in any of three 20-min time periods of sampling after the first hours discharge, the amount of glutamate released into the Dentate gyrus of the fourth group rats (morphine with physical activity) is elevated significantly compared to other groups (p<0.05). In comparison of the control group with the groups of morphine and physical activity, no significant difference was found in any of sampling times (p>0.05).ConclusionTo justify these results, perhaps we can say that morphine would make consistent changes in transmission of glutamatergic synapses and in this way increase its extracellular amount. On the contrary physical activity would decrease its extracellular amount through the elevation of glutamate transmitters (GLTs). Injection of morphine and physical activity thereafter (morphine with physical activity group) interestingly, because of unknown reasons, probably with a synergism effect between two factors (physical activity and morphine) cause a great increase in extracellular glutamate at the dentate gyrus.