Here's a couple of study's: (i got other compounds in the back of my mind as well but lets take a look at ginseng first.
Wild ginseng attenuates repeated morphine-induced behavioral sensitization in rats.
Lee B, Kwon S, Yeom M, Shim I, Lee H, Hahm DH.
Source
Acupuncture and Meridian Science Research Center, College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Korea.
Abstract
Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on treating morphine addiction, we examined the behavioral sensitization of locomotor activity and c-Fos and TH expression in the rat brain using immunohistochemistry. Intraperitioneal injection of WG (100 and 200 mg/kg), 30 min before administration of a daily injection of morphine (40 mg/kg, s.c.), significantly inhibited morphine-induced increases in c-Fos expression in NAc and TH expression in VTA as well as in locomotor activity, as compared with Panax ginseng. It was demonstrated that the inhibitory effect of WG on the behavioral sensitization after repeated exposure to morphine was closely associated with the reduction of dopamine biosynthesis and postsynaptic neuronal activity. It suggests that WG extract may be effective for inhibiting the behavioral effects of morphine by possibly modulating the central dopaminergic system and that WG might be a useful resource to develop an agent for preventing and treating morphine addiction.
Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine.
Seo JJ, Lee JW, Lee WK, Hong JT, Lee CK, Lee MK, Oh KW.
Source
College of Pharmacy, Chungbuk National University, Cheongju, 360-763, Korea.
Abstract
We have reported that ginseng total saponin (GTS) inhibited the development of physical and psychological dependence on morphine. However, the possible molecular mechanisms of GTS are unclear. Therefore, this study was undertaken to understand the possible molecular mechanism of GTS on the inhibitory effects of morphine-induced dependence. It has been reported that the up-regulated cAMP pathway in the LC of the mouse brain after repeated administration of morphine contributes to the feature of withdrawals. GTS inhibited up-regulation of cAMP pathway in the LC after repeated administration of morphine in this experiment. GTS inhibited cAMP levels and protein expression of protein kinase A (PKA). In addition, GTS inhibited the increase of cAMP response element binding protein (CREB) phosphorylation. Therefore, we conclude that the inhibitory effects of GTS on morphine-induced dependence might be mediated by the inhibition of cAMP pathway.
Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats.
Qi D, Zhu Y, Wen L, Liu Q, Qiao H.
Source
Neuroscience Program, Shandong University of Traditional Chinese Medicine, Jinan, China.
Abstract
Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.
Pharmacological action of Panax ginseng on the behavioral toxicities induced by psychotropic agents.
Kim HC, Shin EJ, Jang CG, Lee MK, Eun JS, Hong JT, Oh KW.
Source
Neurotoxicology Program, College of Pharmacy, Kangwon National University, Chunchon, Korea.
Abstract
Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (mu-receptors) and mouse vas deferens (delta-receptors) are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine A2A/ delta-opioid receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.
[Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants].
[Article in Japanese]
Tokuyama S, Takahashi M.
Source
Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
[email protected]
Abstract
Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants were summarized. Analgesic effects of opioids, such as morphine and U-50,488H, were blocked by ginseng in a non-opioid dependent manner. Furthermore, ginseng inhibited the tolerance to and dependence on morphine, and prevented the suppressive effect on the development of morphine tolerance caused by co-exposure to foot-shock stress, but not psychological stress. On the other hand, behavioral sensitization (reverse tolerance to ambulation-accelerating effect) to morphine, methamphetamine (MAP) and cocaine was also inhibited by ginseng. Interestingly, ginseng also inhibited the appearance of the recurrent phenomenon (reappearance of the sensitized state was observed at the time of readministration of MAP and cocaine even after a 30-day discontinuation of drug administration) of the effect of MAP and cocaine. The conditioned place preference of MAP and cocaine was completely blocked by ginseng. These findings provide evidence that ginseng may be useful clinically for the prevention of abuse and dependence of opioids and psychostimulants.
Inhibition by ginseng total saponin of the development of morphine reverse tolerance and dopamine receptor supersensitivity in mice.
Kin HS, Kang JG, Oh KW.
Source
Department of Pharmacology, College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Abstract
1. Ginseng total saponin (GTS), 200 mg/kg i.p. 3 hr prior to morphine, inhibited the development of reverse tolerance to the ambulatory-accelerating effect of morphine. 2. GTS, 200 mg/kg, also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of morphine, 10 mg/kg a day for 7 days. 3. These results suggest that GTS may be useful for the prevention and therapy of the adverse action of morphine.
The effect of Panax ginseng on the development of tolerance to the pharmacological actions of morphine in the rat.
Bhargava HN, Ramarao P.
Source
Department of Pharmacodynamics University of Illinois, Chicago 60612.
Abstract
1. The effect of intraperitoneal administration of Panax ginseng on the development of tolerance to the analgesic and hyperthermic actions of morphine was determined in male Sprague-Dawley rats. Rats were rendered tolerant to morphine to different degrees by the subcutaneous implantation of either four pellets of morphine over a 3-day period or six pellets over a 7-day period. Each pellet contained 75 mg of morphine free base. Rats serving as controls were implanted with placebo pellets. 2. Daily administration of ginseng extract (6.25-50.0 mg/kg) for 3 days inhibited the development of tolerance to the analgesic effect but not to the hyperthermic effect of morphine in the four pellet schedule. 3. In six pellet schedule, daily administration of ginseng extract (25 and 50 mg/kg) for 7 days also inhibited the development of tolerance to the analgesic effect of morphine, but the 100 mg/kg dose had no effect. On the other hand, in six pellet schedule, the administration of ginseng extract (50 and 100 mg/kg) once daily for 7 days inhibited the development of tolerance to the hyperthermic effect of morphine. 4. It is concluded that in appropriate doses,ginseng extract has inhibitory activity on the development of tolerance to the pharmacological actions of morphine.
The effect of ginseng extract on locomotor sensitization and conditioned place preference induced by methamphetamine and cocaine in mice.
Tokuyama S, Takahashi M, Kaneto H.
Source
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University, Japan.
Abstract
Repeated i.p. injections of 2 mg/kg methamphetamine (MA) or 20 mg/kg cocaine at 48-h intervals induced reverse tolerance to their ambulation-enhancing effects (behavioral sensitization). Furthermore, the reappearance of the sensitized state was observed at the time of readministration of MA or cocaine even after a 30-day discontinuation of drug administration. A concomitant injection of ginseng extract (GE), 200 mg/kg, i.p., suppressed the development of reverse tolerance and the reappearance of sensitization to MA and cocaine. Conditioned place preference to MA (1, 2, and 4 mg/kg, i.p.) and cocaine (1, 4, 10, and 20 mg/kg, i.p.), was completely blocked by GE, 200 mg/kg, i.p. combined treatment with MA of cocaine. Meanwhile, spontaneous motor activity and place preference were not affected by GE alone. These results provide evidence that GE may be useful clinically for the prevention of adverse actions of MA and cocaine.
