Objective To study the effects of intervention on physiological and biochemical mechanism of psychodependent drug(heroin)addiction. Methods The rat models of heroin addiction were established by treated with heroin 135 mg/ kg to Wistar rats for 14 days, or treated with reserpine 2. 5 mg/ kg and then heroin, and the intervention effect of reserpine on heroin addiction was assessed. Levels of noradrenaline (NA), adenosine cyclophosphate (cAMP), guanosine cyclophosphate (cGMP) and hydroxybutyric acid (GABA), dopamine (DA) in blood and brain tissue of rats were determined by ELISA. Results The levels of cAMP in the heroin group and reserpine group were increased by 18. 87%and 35. 27%, and the cGMP levels were decreased by 10. 15% and 17. 69%, respectively. NA level in the heroin group was increased by 34. 05% than the control group and decreased by 45. 34% than the reserpine group. The levels of GABA in the frontal cortex (PFC), nucleus accumbens (NAc), thalamus (Thalamus) and amygdala (Amygdala) of the heroin group were reduced by 36. 55%, 40. 35%, 42. 34% and 45. 76%, respectively, compared with the control group ( P <0. 01), while the levels GABA in the four tissues of the reserpine group were increased by 31. 06%, 25. 91%, 49. 32 and17. 97%, respectively ( P < 0. 05, P < 0. 01). The levels of DA in the four tissues of the heroin group and reserpine group were increased by 82. 83%, 68. 19%, 87. 26%, 82. 46% ( P < 0. 01) and 8. 79%, 19. 06%, 21. 65%, 19. 49% ( P <0. 05), respectively, compared with the control group. After heroin and reserpine were given, there were significant differences in the frequency of EEG and ECG in the rats. Conclusions Noradrenaline and dopamine are the key factors to induce heroin addiction in vivo. Reserpine depletes noradrenaline and interferes with the biochemical process of heroin addiction.