Effects of the kappa opioid receptor antagonist MR-2266-BS on the acquisition of ethanol preference

Reinforcing properties of ethanol in neonatal rats: Involvement of the opioid system.

“…Two types of opioid receptors, mu and delta, have been more specifically implicated in reinforcing ethanol effects on adults (Frank, Lindholm, & Raaschou, 1998; Froehlich, Zweifel, Harts, Lumberg, & Li, 1991; Hyytia, 1993; Krishnan-Sarin, Jing, et al, 1995; Krishnan-Sarin, Portoghese, Li, & Froehlich, 1995; Krishnan-Sarin et al, 1998). Despite some evidence with adult rats that kappa opioid receptors may be responsible for maintaining ethanol intake at a low level and a few recent studies implicating kappa receptors as a possible target for therapy in the treatment of alcoholism (Holter, Henniger, Lipkowski, & Spanagal, 2000; Lindholm, Ploj, Franck, & Nylander, 2000; Lindholm, Werme, Brene, & Franck, 2001; Sandi, Borrell, & Guaza, 1998, 1990), involvement of this opioid receptor in appetitive ethanol reinforcement is not generally considered great (Gianoulakis, 1996; Herz, 1997), at least in adults.…”

The Role of Delta Opioid Receptors in Ethanol Consumption and Seeking: Implications for New Treatments for Alcohol Use Disorders

“…Furthermore, administration of the KOP-R agonists, dynorphin1-17 or MR-2266-BS, prior to the first free-choice session following a period of forced ethanol exposure reduced preference for ethanol (Sandi et al, 1988;Sandi et al, 1990). The long-acting benzomorphan opioid compound, bremazocine, which acts as an antagonist at MOP-R and DOP-R and an agonist at KOP-R, was shown to more potently reduce 10% ethanol intake than the nonselective opioid antagonist, naltrexone (Nestby et al, 1999).…”

Structure selectivity relationship studies of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6β-[(4′-pyridyl)carboxamido]morphinan derivatives toward the development of the mu opioid receptor antagonists

“…15 KOR antagonists 5'-guanidinonaltrindole (GNTI), nor-binaltorphimine (norBNI), and (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxamide (JDTic) were demonstrated to have antidepressant and anxiolytic activity. 16–21 It was also suggested that kappa antagonists may find a place to treat alcoholism 22–24 , cocaine 25–28 and nicotine 29 addictions. As a selective DOR antagonist, naltrindole (NTI) was reported to be able to attenuate the discriminative stimulus properties of cocaine 30 , reduce both alcohol and saccharin intake in rats bred for alcohol preference 31 .…”