[Effect of short-term forced exercise on naloxone induced withdrawal symptoms in morphine addicted male rats]

Opioid dependence has been causing limitation in usage of morphine and other opioid drugs in pain control. The aim of this study was to assess the effect of short-term forced exercise on withdrawal syndrome in morphine addicted male rats. This experimental study was done in the physiology research center of Ahwas Jondishapour University of Medical Sciences. Twenty four young male Wistar rats, weighing 200-300gr, were randomly divided into four groups: no addiction and no exercise, no addiction and exercise, addiction and no exercise and addiction and exercise. The exercise groups underwent treadmill forced exercise for ten days. The first five days morphine was administrated [ip] twice daily with increasing dose [5, 10, 20, 40, 50 mg/kg] to addicted groups. Also single dose [50mg/kg] of morphine was administrated to them on the 10[th] day of exercise. After administration of naloxone hydrochloride the withdrawal symptoms were evaluated for 5 minutes. The findings of this study were analyzed by SPSS software and One- way ANOVA [Tukey] test. The findings of this study showed that the withdrawal symptoms was elevated in exercise and addicted groups in comparison with control group [p<0.05, p<0.01]. However, most of withdrawal symptoms decreased in addicted and exercise group in comparison with addicted and no exercise group [p<0.01, p<0.001]. The exercise could increase endogenous opioid and withdrawal symptoms in animals but reduce withdrawal symptoms in addicted and exercise groups compared to addicted and no exercise group. Its mechanism might be related to down regulation and low sensitivity of opioid receptors

[Effect of electrical stimulation and lesion of nucleus accumbens on EEG of intact and addicted rats]

The nucleus accumbens is involved in various functions ranging from motivation and reward to feeding and drug addiction. Some researchers have also suggested that this region has some roles in consciousness. In the present study, the effect of electrical stimulation and lesion of nucleus accumbens on Electroencephalogram waves [EEG] of addict and non-addict rats was investigated. Male wistar rats [weight 190-250 g] were divided into control and addict groups. Addiction was induced by injection of morphine [three times a day and for four days]. Then all rats in both groups were aneasthetized by urethane and stainless steel electrodes were implanted in nucleus accumbens. EEG waves were recorded in three stages of control, after stimulation [130 microA, 100 HZ, every 5 sec for 10 min], and after lesion [0.4 m A, 60 sec] of nucleus accumbens in each group. In addict group alpha and beta waves were increased, while theta and delta waves were decreased compared to intact group. Electrical stimulation and lesion of nucleus accumbens decreased theta waves in intact group and increased beta waves in addict group comparing to the control stages. Although morphine dependency causes increase of high frequency- low voltage waves and decrease of low frequency-high voltage waves, it seems, that nucleus accumbens has no role in variations of brain waves

[ 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 exercise [Treadmill Running] on passive- avoidance learning and memory in morphine dependent male rats

In this research, the effects of treadmill running was studied on the passive avoidance learning and memory [PA] in matured male rats having been morphine dependent. In the behavioral stage, 36 rats weighing about 250g were housed in four groups as follows: Control; Morphine dependent; Exerciser and Exerciser's morphine dependent. Intraperitoneal injection [IP] of solved morphine with increased doses of, respectively; first three-day: 10mg/kg, second three-days 20mg/kg and third three-day, 40mg/kg were applied to make rats morphine-dependent. Treadmill running was performed in a ten-day period [two hours a day, at a speed of 12m/min and a incline of 15 degree] for the two groups of exerciser and exerciser's morphine dependent. Passive avoidance learning and memory test after attending physical exercises and making morphine- dependent were performed in similar conditions for all groups. On the basis of these results, in comparision to the average of the Control group with that of the Exerciser and Exerciser's morphine dependent groups; it is confirmed that physical activity strengthen the indicators of positive criterion [LS and Latency] and weaken the negative criterion [DS]. About the first indicator [Latency]: In the comparison of control group with the two groups of exerciser and exerciser's morphine dependent, a significant increase until 24 hours after footshock, and for the third indicator [LS] until one week after shock and for the second indicator [DS] a significant decrease until one week after shock was observed [***p<0.001, **p<0.01, *p<0.05]. In the meantime, no significant difference was observed for one month after shock [p>0.05].In comparison to control group with morphine-dependent group, except for the second indicator [DS] in which a negative criterion was considered, only a significant increase was observed 24 hours after footshock [p<0.05]. In comparison to the average of the second group [morphine-dependent] with the fourth group [exerciser's morphine-dependent], it was observed that there is a significant difference for Latency indicator until 24 hours after shock and for the indexicator of LS and DS until one week after footshock [+++p<0.001, ++p<0.01, +p0.05]. The result of behavioral steps showed that physical exercises increase the learning rate and strengthen short-term memory [STM] recalling, but it does not have any sensible effect on past event memory. Accordingly, it is said that probably some parts of hippocampus were influenced by physical activity. Moreover, physical exercise had treated the negative effects caused by morphine on the memory and learning in morphine-dependent rats, so that they recalled the past memories in the same way as the control group

Morphine releases glutamate through AMPA receptors in the ventral tegmental area: a microdialysis study in conscious rats

In vivo microdialysis was used to study the effects of morphine on glutamate release from the ventral tegmentum area [VTA] in freely moving rats. Intraperitoneal [i.p.] injection of acute and repeated morphine at increasing doses significantly enhanced glutamate release. Only a minor tolerance developed to this dosage of morphine. AP-5 [2-amino-5-phosphonovaleric acid, 0.5 mg/kg i.p.], a NMDA receptor antagonist, given 20 min before each repeated morphine injection, did not have a significant effect on the stimulated glutamate release. Conversely, injection of CNQX [6-cyano-7-nitroquinoxaline-2, 3-dione, 0.5 mg/kg i.p.], an AMPA receptor antagonist, 20 min before each morphine dose was found to markedly inhibit morphine-induced glutamate release in the VTA. In all experiments, glutamate release reduced by time. These results show for the first time that acute and repeated injection of morphine stimulates glutamate release in the conscious rat VTA via AMPA receptors