RESUMO
The mechanism of drug dependence and tolerance have not been known exactly and several neurotransmitters are involved. The rennin angiotensin system can be effective on reward system and can be interacted wiith different neurotransmitters in the brain. It is possible that the rennin angiotensin system have interaction with opioid system because it has been shown that angiotensin II and ACE inhibitors have analgesic, anticonvulsant and antidepression effects and in some cases they could antagonize morphine effect. In the present study the effect of angiotensin II and captopril on morphine self administration was evaluated in rats. Male wistar rats [250-300 gr] were used. First they have trained to receive small pellets with pressing active lever in self administration apparatus. Then jugular vein was canullated and an stainless style cannula was inserted in the brain right ventricle and fixed with dental sement. after recovery the animals were placed in the self administration apparatus for 11 days and 2 hours in a day. [The first 6 days were with food restriction and the later 5 days were without food rectriction]. The animals received 0.1 ml of morphine and small pellets in first 6 days and only 0.1 ml of morphine in the later 5 days with pressing active lever. the animals received no food morphine with pressing the passive lever. Finally the number of active and passible lever pressing in each group and the number of active pressing among different groups was compared which had been recorded by computer. number of active passive level pressed was significantly different in morphine group [p< 0.01, p< 0.001]. Number of active level pressed in morphine group was significantly higher than that saline group in the final three days [p< 0.05, p<0.001]. In captopril group there was not significant difference between active and passive lever pressed number in the last 5 days and number of active lever pressed was significantly lower than that morphine group [p< 0.05, p< 0.001]. Angiotensin II could not cause any significant change in the number of lever pressed, With consideration that captopril can reduce endogenous opioid degradation it probably could reduce morphine tendency in this way. In The other hand captopril can interact with dopamine, serotonin, substance p, acetylcholine or nitric oxide in the different brain regions and morphine tendence that it needs more investigations