Electroacupuncture Reduces Voluntary Alcohol Intake in Alcohol-preferring Rats via an Opiate-sensitive Mechanism

Bowles Center for Alcohol Studies, UNC School of Medicine, Chapel Hill, NC 27599-7178, USA.
Neurochemical Research (Impact Factor: 2.59). 10/2008; 33(10):2166-70. DOI: 10.1007/s11064-008-9791-9
Source: PubMed


Electroacupuncture (EA) has been shown to modify the effects of various drugs of abuse, including alcohol. Inbred P rats were trained to drink alcohol voluntarily and then subjected to two periods of alcohol deprivation lasting 3 days. During the second deprivation, the rats received either EA or sham EA. The rats were pretreated with naltrexone (5 mg/kg) or saline 30 min before each of the EA or sham EA sessions. Approximately 6 h after the last naltrexone or saline treatment, the alcohol tubes were returned and alcohol and water intakes were recorded later at 2, 4, 6, and 24 h. Only EA led to a decrease in alcohol intake, which was most prominent at 6 and 24 h, and this inhibitory effect of EA was blocked by naltrexone, suggesting that activation of the endogenous opiate system may be responsible for EA's effects on alcohol intake in the alcohol-dependent iP rats.

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    • "Previous studies from our and the other laboratories have shown that chronic alcohol exposures induce the accumulation of ΔFosB within the subregions of the striatum and the prefrontal cortex (PFC) [16], [19], which involves activation of endogenous opioid systems [19]. Given that existing evidence indicates that EA alleviated alcohol consumption and morphine dependence via interacting with opioid receptors [12], [20], [21]; and that acupuncture attenuates stress-induced cocaine relapse by suppressing Fos expression and CREB activation within the subregions of the striatum [22], we hypothesized that EA suppression on alcohol consumption may be mediated by transcription factors, such as FosB/ΔFosB protein in reward-related brain regions. To test this possibility, multiple sessions of EA were administrated at the bilateral acupoint ST36 of rats that chronically drink large quantities of ethanol under a modified intermittent access two-bottle choice drinking procedure (IE). "
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    ABSTRACT: New therapies are needed for alcohol abuse, a major public health problem in the U.S. and worldwide. There are only three FDA-approved drugs for treatment of alcohol abuse (naltrexone, acamprosate and disulfuram). On average these drugs yield only moderate success in reducing long-term alcohol consumption. Electroacupuncture has been shown to alleviate various drugs of abuse, including alcohol. Although previous studies have shown that electroacupuncture reduced alcohol consumption, the underlying mechanisms have not been fully elucidated. ΔFosB and FosB are members of the Fos family of transcription factors implicated in neural plasticity in drug addiction; a connection between electroacupuncture's treatment of alcohol abuse and the Fos family has not been established. In this study, we trained rats to drink large quantities of ethanol in a modified intermittent access two-bottle choice drinking procedure. When rats achieved a stable baseline of ethanol consumption, electroacupuncture (100 Hz or 2 Hz, 30 min each day) was administered at Zusanli (ST36) for 6 consecutive days. The level of FosB/ΔFosB in reward-related brain regions was assessed by immunohistochemistry. We found that the intake of and preference for ethanol in rats under 100 Hz, but not 2 Hz electroacupuncture regiment were sharply reduced. The reduction was maintained for at least 72 hours after the termination of electroacupuncture treatment. Conversely, 100 Hz electroacupuncture did not alter the intake of and preference for the natural rewarding agent sucrose. Additionally, FosB/ΔFosB levels in the prefrontal cortex, striatal region and the posterior region of ventral tegmental area were increased following excessive ethanol consumption, but were reduced after six-day 100 Hz electroacupuncture. Thus, this study demonstrates that six-day 100 Hz electroacupuncture treatment effectively reduces ethanol consumption and preference in rats that chronically drink excessive amount of ethanol. This effect of electroacupuncture may be mediated by down-regulation of FosB/ΔFosB in reward-related brain regions.
    Full-text · Article · Jul 2012 · PLoS ONE
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    • "By activation of μ opioid receptors, low frequency EA may reduce VTA GABAergic inhibitory transmission and increase the activity of VTA DA neurons and the release of dopamine and thus reduce the need for drinking EtOH. This possibility is supported by previous studies showing that EA decreased EtOH drinking behaviors in iP and Wistar rats by activating the endogenous opiate system (Yang et al., 2010; Overstreet et al., 2008). Previous studies have demonstrated that electrical stimulation itself may increase release of opioid peptides. "
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    ABSTRACT: Although there is increasing clinical acceptance of acupuncture and electroacupuncture (EA) as a treatment of substance abuse-related disorders, our understanding of this treatment remains incomplete. Previous clinical and pre-clinical studies have shown that acupuncture and EA are effective in reducing ethanol consumption. Recent studies have shown that Sprague-Dawley (SD) rats under an intermittent-access two-bottle choice drinking procedure (IE procedure) voluntarily drank high amounts of ethanol. However, an effect of EA on ethanol consumption of the SD rats under this drinking procedure has not been demonstrated. In the present study, we demonstrated that SD rats escalated their ethanol intake and subsequently developed ethanol dependence under the IE procedure. A single low (2 Hz), but not high frequency (100 Hz) EA treatment applied at the bilateral acupoint Zusanli (ST36), but not at the tail reduced voluntary intake of, and preference for ethanol, but not sucrose. Furthermore, repeated EA treatments decreased the intake of and preference for ethanol, without resulting in a rebound increase in ethanol intake when the EA treatments were terminated. These observations indicate that EA may be a useful treatment for alcohol abuse.
    Full-text · Article · Aug 2011 · Brain research bulletin
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    ABSTRACT: Since 1994, when naltrexone (Revia) was approved by the FDA for the treatment of alcoholism, only 2 other drugs (Campral and Topamax have been approved for alcoholism treatment. However, various experimental drugs, including antiepileptic medications, have been tested in both animal models and in humans with some promising results. The purpose of this project was to study the effect of the novel neuromodulator carisbamate, which is in development for epilepsy treatment, on alcohol intake in selectively bred alcohol-preferring rats. Male alcohol-preferring inbred P rats were allowed to freely drink water or alcohol (10%, v/v) using a 2-bottle choice procedure. After stable baselines for alcohol and water intakes were established, the acute effects of oral carisbamate (0, 10, 30, 45, 60, and 90 mg/kg) were assessed. Then, the chronic effect of the compound (60 mg/kg/day for 14 consecutive days) on alcohol intake was assessed in a separate group of male P rats. In another set of experiments, the effects of carisbamate and naltrexone on alcohol withdrawal-induced elevated drinking of alcohol, an index of craving, were compared. Rats were withdrawn from alcohol for 24 hours and were given vehicle, 20 mg/kg naltrexone or 60 mg/kg carisbamate 30 minutes before re-exposure to alcohol. Alcohol and water intake was measured 6 hours after alcohol re-exposure. To determine the effects of carisbamate on saccharin preference, rats were put on a 2-bottle choice of water versus a solution of 2% saccharin. Then, the effect of the highest dose of carisbamate (90 mg/kg) and naltrexone (20 mg/kg) and the vehicle on saccharin preference was determined. Our results showed that there was a selective dose-dependent reduction in alcohol intake and preference in the alcohol-preferring P rat after an acute oral administration of carisbamate. There were no significant effects on food or water intake. Chronic administration of carisbamate significantly reduced alcohol intake and preference initially, but partial tolerance developed after the 10th treatment. The degree of tolerance development was less than that observed for naltrexone. Acute administration of carisbamate was more effective than naltrexone in reducing enhanced alcohol intake after a period of alcohol deprivation. Compared with control vehicle neither carisbamate nor naltrexone had a significant effect on saccharin intake and preference. The novel neuromodulator compound carisbamate has a favorable profile of effects on alcohol intake and related measures and should be considered for testing on human alcoholics.
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