Abstract
Effects of the opioid receptor like-1 (ORL-1) receptor agonist Ro 64-6198 (0.1, 0.3, and 1.0 mg/kg intraperitoneally (i.p.)) on operant ethanol self-administration and activation of self-administration by ethanol deprivation were studied in male Wistar rats. Acute administration of Ro 64-6198 caused a dose-dependent reduction of ethanol self-administration. In comparison, the opioid antagonist naltrexone (0.1, 0.3, and 1.0 mg/kg i.p.) inhibited ethanol self-administration at all doses tested. Ethanol deprivation for 10 days significantly increased ethanol self-administration during the first 2 days after deprivation. Daily pretreatment with Ro 64-6198 (0.3 mg/kg) or naltrexone (0.3 mg/kg) during the last 3 days of ethanol deprivation abolished the deprivation-induced increase in ethanol intake. Thus, stimulation of the ORL-1 receptors by Ro 64-6198 reduced the acute reinforcing effects of ethanol and prevented relapse-like behavior in the ethanol-deprivation model in a similar manner as a blockade of opioid receptors by naltrexone. Ro 64-6198 at 0.1 and 0.3 mg/kg doses did not alter self-administration of 0.2% saccharin solution, indicating an apparent selectivity of this compound in modification of ethanol reward. These findings add further support to the idea that Ro 64-6198 and potentially other synthetic ORL-1 receptor agonists are as effective as naltrexone in blocking the actions of ethanol important for its addictive potential in animal experiments, and therefore may have therapeutic value in the treatment of alcoholism.
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Acknowledgements
We are grateful to Dr Ann Ho for help with statistical analysis. This work was supported by the National Institutes of Health and National Institute on Drug Abuse (Grant K05-DA00049) to MJK, the Swedish Foundation at Alcohol Research and Karolinska Institutet to AK, SL, and GB, the Swedish AFA Foundation to GB and AK, and the Swedish Science Research Council to GB and SL. We thank Dr F Jenck and Dr J Wichmann, Hoffmann-La Roche Ltd, Basel, Switzerland, for the generous gift of the synthetic nociceptin agonist Ro 64-6198.
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Kuzmin, A., Kreek, M., Bakalkin, G. et al. The Nociceptin/Orphanin FQ Receptor Agonist Ro 64-6198 Reduces Alcohol Self-Administration and Prevents Relapse-Like Alcohol Drinking. Neuropsychopharmacol 32, 902–910 (2007). https://doi.org/10.1038/sj.npp.1301169
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