-Original-

Rewarding Effects of Ethanol Combined with Low Doses of Morphine through Dopamine D1 Receptors

Yuya Ise^1,2, Tomohisa Mori², Shirou Katayama¹, Hiroshi Nagase³ and Tsutomu Suzuki²

¹Section of Pharmaceutical Services, Nippon Medical School Hospital
²Department of Toxicology, Hoshi University, School of Pharmacy and Pharmaceutical Science
³Laboratory of Medical Chemistry, School of Pharmacy, Kitasato University

This study investigated whether ethanol combined with low doses of morphine produces rewarding effects in rats. Ethanol (0.075-1.2 g/kg, intraperitoneal [i.p.]) alone did not induce place preference. A moderate dose (1 mg/kg, s.c.), but not a low dose (0.1 mg/kg), of morphine induced a significant place preference. The combination of ethanol (0.075-0.6 g/kg, i.p.) and 0.1 mg/kg of morphine, as well as low doses of morphine (0.03-0.1 mg/kg, subcutaneous [s.c.]) combined with ethanol (0.3 g/kg, i.p.), induced a significant place preference. The combined effect of ethanol and morphine was significantly attenuated by naloxone (0.3 mg/kg, s.c.), naltrindole (1.0 mg/kg, s.c.), or long-term administration of the dopamine D1 receptor antagonist SCH23390 (1.0 mg/kg/day, s.c.). These results suggest that the rewarding effect induced by ethanol and a low dose of morphine is mediated by activation of the central opioidergic and dopaminergic systems through dopamine D1 receptors.

J Nippon Med Sch 2013; 80: 34-41

Keywords
ethanol, morphine, conditioned place preference, rats

Correspondence to
Tsutomu Suzuki, PhD, Department of Toxicology, Hoshi University, School of Pharmacy and Pharmaceutical Science, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
Suzuki@hoshi.ac.jp

Received, May 14, 2012
Accepted, August 10, 2012