The Effects of Angiotensin II and Captopril on Expression of Morphine Withdrawal Signs in Rat

The mechanisms of drug dependence and rewarding properties of opiates are not exactly known and several neurotransmitters seem to be involved. It is possible that the rennin-angiotensin system could interact with the opioid system, since it has been shown that angiotensin II(Ang) and ACE inhibitors have analgesic, anticonvulsant and antidepression effects and in some cases they could antagonize the effect of morphine. In the present study, the effect of Ang II and captopril on withdrawal signs was evaluated.

Male wistar rats were anesthetized and i.c.v cannula implanted and allowed to recover from surgery. Morphine was injected (i.p, 3 times a day) for 4 days to induce morphine dependence. The animals were divided into 3 groups and received saline, captopril, Ang II, and i.c.v, before naloxone injection. Naloxone precipitated morphine withdrawal signs, compared to the morphine dependent rats in saline, captopril and Ang II groups.

Results showed that in the captopril group, some of the withdrawal signs were significantly lower than the saline group (p<0.05 and p<0.01). In the Ang II group, some of the withdrawal signs were greater than the saline group (p<0.01 and p<0.001).

Considering the fact that captopril can reduce endogenous opioid degradation, it could probably reduce the morphine withdrawal signs in this way. On the other hand, captopril and Ang II can interact with dopamine, serotonin, substance p, acetylcholine or nitric oxide in different brain regions and alter morphine withdrawal signs.