Addiction-related interactions of pregabalin with morphine in mice and humans: reinforcing and inhibiting effects.

Autor: Vashchinkina E; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Piippo O; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Vekovischeva O; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland., Krupitsky E; Department of Addictions, St. Petersburg Bekhterev Research Psychoneurological Institute, St. Petersburg, Russia., Ilyuk R; Department of Addictions, St. Petersburg Bekhterev Research Psychoneurological Institute, St. Petersburg, Russia., Neznanov N; Department of Addictions, St. Petersburg Bekhterev Research Psychoneurological Institute, St. Petersburg, Russia., Kazankov K; Murmansk Regional Addiction Hospital, Murmansk, Russia., Zaplatkin I; Murmansk Regional Addiction Hospital, Murmansk, Russia., Korpi ER; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Jazyk: angličtina
Zdroj: Addiction biology [Addict Biol] 2018 May; Vol. 23 (3), pp. 945-958. Date of Electronic Publication: 2017 Jul 25.
DOI: 10.1111/adb.12538
Abstrakt: The gabapentinoid pregabalin is a rapid-acting anxiolytic and analgesic, possibly suitable in supervised opioid detoxification. However, clinicians have been cautious in using it because of its unknown addictive risk and rising number of mortalities after pregabalin self-medication in opioid abusers. Here, we studied interactions of pregabalin and morphine on reward functions of the dopamine system in mice and the efficacy of pregabalin on withdrawal in opioid addicts. After the treatment of mice with pregabalin and morphine, we used electrophysiology to study neuroplasticity in midbrain slices, self-administration and conditioned place preference tests to investigate the rewarding potential of pregabalin and naloxone-precipitated morphine withdrawal to evaluate opioid withdrawal symptoms. Further, we ran a pilot single-blind, randomized, controlled trial (34 heroin addicts) to evaluate the efficacy and safety of pregabalin in the treatment of opioid withdrawal syndrome. Pregabalin alone did not induce glutamate receptor neuroplasticity of dopamine neurons in the ventral tegmental area, but pre-treatment with pregabalin suppressed morphine-induced neuroplasticity, hyperlocomotion and morphine self-administration. Pregabalin administration after chronic morphine exposure failed to induce any rewarding effects. Instead, pregabalin suppressed withdrawal symptoms in both morphine-treated mice and opioid addicts and was well tolerated. Intriguingly, pregabalin administration after a low dose of morphine strongly facilitated ventral tegmental area neuroplasticity and led to increased conditioned place preference. Pregabalin appears to have the efficacy to counteract both reinforcing and withdrawal effects of opioids, but it also has a potentiating effect when given to mice with existing opioid levels.
(© 2017 Society for the Study of Addiction.)
Databáze: MEDLINE
Externí odkaz: