Elsevier

Neuroscience Letters

Volume 431, Issue 3, 6 February 2008, Pages 221-225
Neuroscience Letters

Effect of chronic acamprosate treatment on voluntary alcohol intake and β-endorphin plasma levels in rats selectively bred for high alcohol preference

https://doi.org/10.1016/j.neulet.2007.11.041Get rights and content

Abstract

Our previous studies have shown that repeated acamprosate administration to ethanol-naive Warsaw high preferring (WHP) rats resulted in increased plasma β-endorphin levels and at least partially prevents increases in levels of this peptide after a single administration of ethanol compared with untreated control rats. The objective of the present study, which included 45 WHP rats, was to continue the past research and investigate the effect of 10-day acamprosate treatment (200 mg/kg p.o.) on alcohol intake using a free-choice procedure and on changes in plasma β-endorphin levels while alcohol is available, and 10 days after alcohol withdrawal. Voluntary alcohol consumption increases plasma levels of β-endorphin from 440 ± 25 pg/ml to 711 ± 57 pg/ml (p = 0.0002). After a 10-day of alcohol withdrawal, the levels of this peptide were significantly reduced compared with levels in rats with free access to ethanol (711 ± 57 pg/ml vs. 294 ± 38 pg/ml, p = 0.000001) and in control naive rats (440 ± 25 pg/ml vs. 294 ± 38 pg/ml, p = 0.044). Chronic treatment with acamprosate increased plasma β-endorphin levels both in WHP rats with free access to ethanol (440 ± 25 pg/ml vs. 616 ± 49 pg/ml, p = 0.008) and in rats after ethanol withdrawal (440 ± 25 pg/ml vs. 620 ± 56 pg/ml, p = 0.007). In the group with free access to ethanol, there was a significant reduction in mean ethanol intake, from 6.75 ± 0.20 g/kg body weight/day to 4.68 ± 0.25 g/kg/day. Our results indicate that chronic acamprosate treatment may have beneficial effects, as it increases the β-endorphin concentration thereby compensating for β-endorphin deficiency during ethanol withdrawal. As the endogenous opioid system has an important role in the development of craving for alcohol, restoring the alcohol-induced deficits in β-endorphin levels may be an important factor to prevent craving and maintaining abstinence. We suppose that the anti-craving mechanism of acamprosate that has been reported to abolish excessive glutamate release during alcohol withdrawal may be accompanied by compensation for the β-endorphin deficiency.

Section snippets

Acknowledgements

This study was supported by the Medical University of Lodz, Poland (grants 502-13-490 and 503-3011-1).

References (48)

  • J.M. Van Ree

    Endorphins and experimental addiction

    Alcohol

    (1996)
  • F. van Haaren et al.

    Sex differences in schedule-induced alcohol consumption

    Alcohol

    (1994)
  • J. Zalewska-Kaszubska et al.

    Changes in the beta endorphin plasma level after repeated treatment with acamprosate in rats selectively bred for high and low alcohol preference

    Neurosci. Lett.

    (2005)
  • M. Almaric et al.

    Rewarding properties of beta-endorphin as measured by conditioned place preference

    Psychopharmacology

    (1987)
  • F.E. Bloom

    The endorphins: a growing family of pharmacologically pertinent peptides

    Ann. Rev. Pharmacol. Toxicol.

    (1983)
  • C. Bouza et al.

    Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review

    Addiction

    (2004)
  • M.S. Cowen et al.

    The acute anti-craving effect of acamprosate in alcohol-preferring rats is associated with modulation of the mesolimbic dopamine system

    Addict. Biol.

    (2005)
  • X. Dai et al.

    Differences in the peripheral levels of beta-endorphin in response to alcohol and stress as a function of alcohol dependence and family history of alcoholism

    Alcohol. Clin. Exp. Res.

    (2005)
  • P. De Witte et al.

    Neuroprotective and abstinence-promoting effects of acamprosate. Elucidating the mechanism of action

    CNS Drugs

    (2005)
  • G. Di Chiara

    Alcohol dopamine

    Alcohol Health Res. World

    (1997)
  • W. Dyr et al.

    Animal model of ethanol abuse: rats selectively bred for high and low voluntary alcohol intake

    Acta Pol. Pharm. Drug Res.

    (2000)
  • W. Dyr et al.

    Preliminary phenotypic characterization of the Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) lines of rats selectively bred for high and low ethanol consumption

    Pol. J. Pharmacol.

    (2004)
  • J.C.W. Finley et al.

    Immunocytochemical localization of β-endorphin-containing neurons in the rat brain

    Neuroendocrinology

    (1981)
  • C. Gianoulakis

    Endogenous opioids and addiction to alcohol and other drugs of abuse

    Curr. Top. Med. Chem.

    (2004)
  • Cited by (14)

    • Unconventional anxiety pharmacology in zebrafish: Drugs beyond traditional anxiogenic and anxiolytic spectra

      2021, Pharmacology Biochemistry and Behavior
      Citation Excerpt :

      Administered alone, naloxone evokes no behavioral activity in mammals (Belzung and Agmo, 1997; Belzung and Ågmo, 1997), but induces anxiogenic-like bottom swimming with frequent short hyperactivity bouts in zebrafish (Stewart et al., 2011). These findings suggest that opioid antagonists can trigger anxiety in zebrafish by non-selectively inhibiting endogenous opioids (that, in turn, may have higher baseline levels in fish vs. mammals, see Nakao et al., 1978; Pottinger et al., 1995; Zalewska-Kaszubska et al., 2008 for details). For instance, baseline plasma β-endorphin levels are 5-fold higher in some teleost fish (e.g., rainbow trout) (Pottinger et al., 1995) than in rats (Zalewska-Kaszubska et al., 2008), and are >100-fold higher than in humans (Nakao et al., 1978).

    • Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with lamotrigine

      2015, Physiology and Behavior
      Citation Excerpt :

      Perhaps the lack of effect of lamotrigine on the opioid system, as seen by Hajhashemi and Abed-Natanzi [39] was the reason for its ineffectiveness in suppression of naloxone-precipitated opiate withdrawal syndrome. In contrast to lamotrigine, topiramate, which was effective in the above test, affects the opioid system similarly to acamprosate and naltrexone, the most effective drugs in the treatment of alcohol addiction [40,41]. In the present study we have observed that the beta-endorphin level, in rats without access to ethanol, didn't change and was similar both in groups treated and untreated with lamotrigine.

    • Acamprosate {monocalcium bis(3-acetamidopropane-1-sulfonate)} reduces ethanol-drinking behavior in rats and glutamate-induced toxicity in ethanol-exposed primary rat cortical neuronal cultures

      2013, European Journal of Pharmacology
      Citation Excerpt :

      The daily dose of 200 mg/kg acamprosate used in the present study is greater than the clinical dose of about 40 mg/kg daily used for the treatment of alcohol dependence. However, a dose of 200 mg/kg is commonly used to study the effect of this compound in animal models (Gupta et al., 2008; Olive et al., 2002; Spanagel et al., 1996; Zalewska-Kaszubska et al., 2008). Acamprosate reduced ethanol consumption during the treatment period, and the reduction was significant from day 6 to day 8 and from day 11 to day 15 (Fig. 1B and Table 1).

    • Voluntary alcohol consumption and plasma beta-endorphin levels in alcohol preferring rats chronically treated with levetiracetam: A preliminary study

      2011, Physiology and Behavior
      Citation Excerpt :

      Our previous studies demonstrated that repeated treatment with acamprosate and naltrexone, the most effective drugs in the treatment of alcohol addiction, resulted in an increase of beta-endorphin concentrations in the rats' plasma. The beta-endorphin increase was accompanied by a decrease in voluntary alcohol intake by alcohol preferring rats [15,16]. We have also found that topiramate increases the levels of beta-endorphin [17].

    View all citing articles on Scopus
    View full text