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275 results on '"Liljequist, Sture"'

40. Repeated moderate-dose ethanol bouts impair cognitive function in Wistar rats

Author

Kuzmin, Alexander, Liljequist, Sture, Meis, Jennifer, Chefer, Vladimir, Shippenberg, Toni, and Bakalkin, Georgy

Subjects
Male, Analysis of Variance, Azides, Time Factors, Alcohol Drinking, Dose-Response Relationship, Drug, Ethanol, Central Nervous System Depressants, Water, Article, Rats, Substance Withdrawal Syndrome, Benzodiazepines, Disease Models, Animal, Cognition, Memory, Animals, Rats, Wistar, Cognition Disorders, Maze Learning
Abstract

The effects of repeated, intermittent administration of a moderate dose of ethanol (3.4 g/kg/day × 6 days, intragas-trically via gavages) on cognitive function were examined in male Wistar rats. No significant differences in weight gain between the ethanol- and water-treated rats were found. Analysis of physical dependence revealed no signs of spontaneous withdrawal, whereas withdrawal signs exacerbated by Ro15-4513, an inverse benzodiazepine agonist, were apparent 5 hours but not 24 hours after the cessation of ethanol treatment. Spatial learning and memory, as assessed in the Barnes maze, were impaired 3–6 days following the treatment but recovered by the 11th–14th days. Reversal learning, however, was impaired throughout the 2-week observation period. Thus, bouts of moderate-dose ethanol administration transiently impair spatial learning and memory, and promote cognitive inflexibility. The employed ethanol exposure paradigm may provide a model of human cognitive deficits associated with alcohol binge drinking.

Published
2011

44. The nociceptin/orphanin FQ receptor agonist Ro 64-6198 reduces alcohol self-administration and prevents relapse-like alcohol drinking

Author

Kuzmin, Alexander, Kreek, Mary Jeanne, Bakalkin, Georgy, Liljequist, Sture, Kuzmin, Alexander, Kreek, Mary Jeanne, Bakalkin, Georgy, and Liljequist, Sture

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.

Published
2007
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