Effects of angiotensin II and captopril on morphine self-administration and withdrawal signs in rats

Abstract

The aim of this study was to investigate the effects of Ang II and captopril on altering the motivational aspects during the initiation of morphine self-administration. Male Wistar rats were first trained to receive small pellets of food by pressing the active lever in self-administration apparatus. They were anaesthetized with Ketamine and their jugular vein was cannulated. The stainless steel cannula was also inserted into the right brain ventricle and fixed with dental cement. After recovery, the animals were divided into 4 groups (saline, morphine, captopril and Ang II) and placed in self-administration apparatus and allowed to self-administer morphine (1.7 mmol per infusion all test groups) or saline (saline group) during 11 consecutive days for 2 h/sessions. Captopril (300 mmol) and Ang II (1 nmol) injected (i.c.v.) in the corresponding groups before each session. The number of active and passive levers pressed in each group was recorded. After the last session, morphine withdrawal signs were recorded following naloxone injection. In morphine group, the number of active lever pressing was significantly higher than passive one in all 11 days (p<0.01) and was also significantly higher than the saline group in the final three days (p<0.05). In captopril group, there were no significant differences between the number of active and passive lever pressings during free access to food (last 5 days). However, the number of active lever pressing was significantly lower than morphine group (p<0.05). Some of the withdrawal signs decreased and increased significantly in captopril and Ang II groups, respectively. This study implies the interaction between captopril and opioid system. © 2008 Asian Network for Scientific Information.