A Possible Mechanism Underlying the Effectiveness of Acupuncture in the Treatment of Drug Addiction

Chae Ha Yang; Bong Hyo Lee; Sung Hoon Sohn

Disclosures

Evid Based Complement Alternat Med. 2008;5(3):257-266. 

In This Article

Role of κ-opioid Receptor in Acupuncture

A number of studies with rats have shown that acupuncture attenuates rewarding effects induced by drugs of abuse. Recent work using injections of selective opioid receptor antagonists has shown that κ-receptor may be particularly important for the inhibitory effect of high-frequency electroacupuncture on the expression of morphine-induced CPP and cocaine-induced CPP.[90,91] High-frequency electroacupuncture increases dynorphin release to interact with κ-receptor in brain.[92] A similar observation was obtained in another study in which high-frequency electroacupuncture enhanced the expression of mRNA encoding predynorphin in brain.[93] Recent studies have demonstrated that dynorphin causes the decrease in dopamine release within the nucleus accumbens through an action on κ-opioid receptors that are located on presynaptic dopaminergic nerve terminals in this region.[93,94] Furthermore, behavioral studies reported that κ-opioid receptor agonists decrease cocaine and heroin self-administration.[95,96] Therefore, it has been suggested that high-frequency electroacupuncture stimulation is sufficient to dampen morphine-induced CPP through κ-opioid receptor. Roles for enkephalin and dynorphin in the mechanisms underlying the inhibitory effect of electroacupuncture has been replicated using morphine-induced CPP and reinstatement of extinguished CPP.[97] Preproenkephalin or preprodynorphin mRNA levels in the nucleus accumbens were increased, respectively, in rats shown to suppress morphine-induced CPP and reinstatement of extinguished CPP after low- or high-frequency electroacupuncture.

Inhibition of Dopamine Release by Acupuncture

There is evidence that the enhancement of dopamine transmission in the nucleus accumbens induced by all addictive drugs is linked to its reinforcing properties and may be implicated in the development of behavioral sensitization.[98,99] This persistent phenomenon, referred to by some as sensitization, is thought to play a major role in magnifying the positive-reinforcing properties of a subsequent drug challenge and represent the mechanism, at least in part, underlying the reinstatement of drug-seeking behavior.[100] Thus, there is lot of interest in gaining a better understanding of how acupuncture works in the brain to influence addictive behaviors. Few studies were designed to investigate the effect of acupuncture on extracellular dopamine levels using in vivo microdialysis and behavioral changes in rats treated by repeated drugs, including morphine and alcohol after drug withdrawal followed by drug challenge. Results showed that systemic challenge with drug produced neurochemical and behavioral sensitization indicating a much larger increase in dopamine and behavioral activity compared to saline-pretreated rats. Most importantly, these results demonstrated that even brief (1 min) acupuncture treatments prevented to a great extent, drug-induced elevation in dopamine levels in the nucleus accumbens and also reduced the amount of drug-induced behavioral hyperactivity.[19,83] In view of the fact that enhanced dopamine transmission in the nucleus accumbens induced by all addictive drugs has long been associated with addictive behaviors, these results suggest that reduction in behavioral activity by acupuncture may be mediated by attenuation of dopamine release and neuronal activity in the nucleus accumbens. Moreover, in a more general sense these results suggest that minimizing sensitization may be one of mechanisms whereby acupuncture reduces drug craving in addicts.

Fewer studies have been performed to determine the basic mechanism underlying acupuncture's effectiveness in reducing dopamine release induced by the drugs. One study used rats to investigate the possible mechanism of acupuncture on the GABAB pathway. Rats were administered with the highly selective GABAB antagonist SCH 50911 prior to an intraperitoneal injection of ethanol. Immediately after ethanol treatment, acupuncture was administered for 1 min. Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly decreased dopamine release in the nucleus accumbens. Inhibition of dopamine release by acupuncture was completely prevented by SCH 50911.[101] GABAergic neurons are known to dampen dopamine neurons via inhibitory GABAB receptors in the mesolimbic dopamine system.[102] Recently, the GABAB receptor agonist reduced reinforcing properties of ethanol.[103] These earlier-mentioned results suggest that stimulation of specific acupoints inhibits ethanol-induced dopamine release by modulating GABAB activity and implies that acupuncture may be effective in blocking the reinforcing effects of ethanol (Fig. 1).

As with cocaine, amphetamines and morphine, addiction to nicotine is believed to result from increased release of dopamine in the region of nucleus acumbens.[104,105] One study reported the effect of acupuncture on behavioral locomotor activity and c-fos expression in the nucleus accumbens and striatum utilizing the immunocytochemical detection of the Fos protein in nicotine-sensitized rats. Similar to morphine or ethanol-sensitized rats, acupuncture significantly attenuated expected increase in nicotine-induced locomotor activity and FLI in the nucleus accumbens and striatum to subsequent nicotine challenge.[106] These findings suggest that acupuncture produces a therapeutic effect on nicotine addiction, possibly by modulating post-synaptic neuronal activity in the nucleus accumbens and the striatum.

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