Suppressive effects of Rosa damascena essential oil on naloxone-precipitated morphine withdrawal signs in male mice

This research was done to test the effect of Rosa damascena essential oil on withdrawal signs of naloxone-precipitated morphine in male mice. Morphine dependence was induced by injection [IP] three times daily at doses of 50, 50 and 75 mg/kg, respectively, for 3 days. On day 4, after the last administration of morphine, Rosa damascena essential oil was administered at different concentrations [5, 2 and 40%, IP] 30 min before administration of naloxone [5 mg/kg, IP]. The following actions were taken as signs of withdrawal and records taken for jumping as a number and scores of 0 to 3 were given for incidences of grooming, teeth chattering, rearing, writing, diarrhea, wet dog shakes and climbing during a 30 min period. Results showed that different concentrations of Rosa damascena essential oil significantly reduced signs of morphine withdrawal compared to the control group in terms of number of jumps [p < 0.05 and p < 0.01], grooming, teeth chattering, rearing, climbing, wet dog shakes and writhing, but not for diarrhea [p < 0.05]. In conclusion it seems that GABAergic activity induced by flavonoids from Rosa damascena essential oil can alleviate signs of morphine withdrawal, but further studies need to be done to better understand this mechanism

[ effect of renin-angiotensin system on morphine tendency in Rats]

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

effects of piperine on the jumping induced by naloxone in morphine dependent mice

Black pepper has been used in traditional medicine as an analgesic. In this investigation, the effects of piperine, an alkaloid derived from black pepper seeds on the jumping induced by naloxone were studied on morphine dependent mice. This experimental study was conducted on case [piperine] and control [saline] groups of mice. Mice were made dependent to morphine using Marshall method. For evaluation of dependency, the number of jumps after naloxone injection was counted in a period of 30 minutes. There was a significant difference between number of jumps of mice in saline [10 ml/kg, IP] and drug groups [piperine 25, 50, 75 mg/kg, IP], as well as significant differences in latency period for jumping behavior in two groups. Based on these results, piperine may affect the intensity of morphine dependency

study of verapamil on morphive dependent animals

The effects of verapamil on naloxone precipitated effects of morphine-dependent guinea pigs ileum were studied in vitro. Dependence was produced in experimental animals by repeated administration of morphine for 15 days. Non-dependent animals given saline for the same period were taken as controls. Verapamil effectively blocked the naloxone induced contractions in ileal strips of morphine-dependent animals. These observations on animal tissues are significant and may suggest clinical usefulness of verapamil in the management of morphine-dependent patients

Effects of antidepressants on morphine withdrawal

The acute and chronic effects of paroxetine and fluoxetine on naloxone- withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluoxetine [25 mg/kg, s.c., given 30 min prior to naloxone withdrawal pairing] and chronic daily paroxetine [10 mg/kg, s.c.] co-administration with a morphine induction protocol, both attenuated morphine withdrawal place aversion. Conversely, acutely administered paroxetine [up to 25 mg/kg, s.c.] or chronic daily fluoxetine [10 mg/kg, s.c.] co-administration with morphine did not modify subsequent withdrawal place aversion. Previous radiologand binding studies have indicated that fluoxetine has opioid-displacing properties. It is suggested therefore that acute fluoxetine may have decreased withdrawal aversion, probably through serotonin and also, in part, via an opioid-like mechanism whereas chronic paroxetine decreased withdrawal aversion by a serotonergic mechanism, but it is not clear whether opioid systems play any role in the action of paroxetine

Failure of reversal of cardiovascular responses of clonidine by centrally administered naloxone in anaesthetised rats.

Central effects of naloxone on the cardiovascular responses of centrally administered clonidine were studied in anaesthetised normotensive, renal DOCA-salt hypertensive and morphine dependent rats. Clonidine (5 micrograms/ICV) produced significant decrease in blood pressure and heart rate in all the groups of rats in a dose dependent manner. Naloxone (2 micrograms/ICV) failed to reverse the responses of clonidine in all the rat groups. In morphine dependent normotensive and morphine dependent renal DOCA-salt hypertensive rats, the responses of clonidine were further enhanced in the presence of naloxone. Our observations clearly indicate that clonidine does not influence endogenous opioid system for producing cardiovascular effects.