Interactive reportSuppression of morphine withdrawal by electroacupuncture in rats: dynorphin and κ-opioid receptor implicated
Introduction
Dynorphin A (1–17) is an endogenous opioid peptide distributed throughout the central nervous system 1, 2, suggesting that it might serve multiple regulatory functions [3]. Our previous work has demonstrated that analgesia induced by 100-Hz electroacupuncture (EA) or 100-Hz transcutaneous electrical nerve stimulation (TENS) was produced by accelerating the release of dynorphin from the spinal cord of the rats [4]and humans [5]. We have also shown that 100-Hz EA was capable of suppressing the morphine withdrawal syndrome in rats [6]and 100-Hz TENS was very effective in ameliorating the withdrawal syndrome in heroin addicts [7]. Although it has been reported that the dynorphin content in the spinal cord was decreased during morphine-dependent and protracted abstinence [8], there were no published data dealing with the issue whether the release of spinal dynorphin is altered during morphine dependent in rats. The first purpose of the current study was to investigate whether 100-Hz EA would induce an analgesic effect in morphine-dependent rats as was the case in normal rats, and whether the effect was mediated by dynorphin via the κ-opioid receptor in spinal cord. The second purpose was to determine whether 100-Hz EA would increase the release of the spinal dynorphin in morphine-dependent rats, and whether the dynorphin is responsible for suppressing the morphine withdrawal syndrome via activation of κ-opioid receptor in the spinal cord. In brief, the aim of this study was to clarify a possible mechanism for the suppression of morphine withdrawal syndrome by 100-Hz EA stimulation in rats.
Section snippets
Animals and experimental design
Adult male Wistar rats weighting 250–300 g were obtained from the Laboratory Animal Center, Beijing Medical University in batches, with food and water ad libitum in the home cage. Three batches of rats were used during the whole study. The first batch of 32 rats were randomly divided into four groups (one control group and three morphine-dependent groups) of eight rats. They were given 100-Hz EA stimulation to induce an analgesic effect. The second batch of 26 rats were randomly divided into
100-Hz EA-induced analgesia in morphine-dependent rats
The basal TFL of the rats was 4.96±0.13 s in the NS control group (n=8) and 3.76±0.14 s in morphine-dependent group (n=24), tested 24 h after the last morphine injection. The latter was markedly lower than the former (100:76, P<0.001). The morphine-dependent rats were randomly divided into three groups of eight rats and given injection of NS or NX (at 1 and 20 mg/kg, s.c.), respectively. Ten minutes after the injection, all the three groups of morphine-dependent rats as well as the NS control
Discussion
Previous studies have shown that 100-Hz EA or TENS can be used for the treatment of opiate dependence with considerable success both in animals [6]and in humans [7]. This would naturally lead to several questions of theoretical interest.
Acknowledgements
The authors wish to thank Dr. Avram Goldstein for his generous help with the dynorphin A antiserum IgG. This work was supported by NIH grant DA 03983, USA, to Ji-Sheng Han, and a grant (39570682) from the National Natural Science Foundation of China to Liu-Zhen Wu.
References (27)
- et al.
Dynorphin immunocytochemistry in the rats central nervous system
Peptides
(1982) - et al.
Suppression of morphine abstinence syndrome by body electroacupuncture of different frequencies in rats
Drug Alcoh. Depend.
(1993) - et al.
Heroin addicts treated with transcutaneous electrical nerve stimulation of identified frequencies
Regulatory Peptides
(1994) - et al.
The effect of morphine tolerance dependence and abstinence on immunoreactive dynorphin(1–13) levels in discrete brain regions, spinal cord, pituitary gland and peripheral tissue of the rats
Brain Res.
(1992) - et al.
Effect of κ-opioid receptor agonists on morphine analgesia in morphine-naive and morphine-tolerant rats
Eur. J. Pharmacol.
(1988) - et al.
Modulation of acute morphine tolerance by corticotriopin-releasing factor and dynorphin A in the mouse spinal cord
Life Sci.
(1992) - et al.
Suppression of withdrawal syndrome by dynorphin in heroin addicts
Eur. J. Pharmacol.
(1982) - et al.
Dynorphin(1–13) attenuate withdrawal in morphine-dependent rats: effect of route of administration
Eur. J. Pharmacol.
(1988) - et al.
Parallel distribution of immunoreactive α-neo-endophin and dynorphin in rat and human tissue
Neuropeptides
(1982) - et al.
Pharmacology of dynorphin
Annu. Rev. Pharmacol. Toxicol.
(1988)
Low and high frequency electroacupuncture stimulations release (Met5) enkephalin and dynorphin A in rat spinal cord
Chin. Sci. Bull.
Effect of low and high frequency TENS on met-enkephlin-Arg-Phe and dynorphin A immmunoreactivity in human lumbar CSF
Pain
Rat tail flick acupuncture analgesia model
Chinese Med. J.
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