In the present study, we examined the development of environment- independent and environment-dependent tolerance to ethanol-induced analgesia (EIA) and cross-tolerance with morphine-induced analgesia (MIA). To examine the development of environment-independent tolerance, male Long-Evans rats were given increasing amounts of ethanol (5 days each of 5% (v/v), 10% (v/v), and 15% (v/v)) added to their drinking water over a 15-day period. A control group was given plain tap water to drink. On day 16, all rats were given plain tap water to drink. On day 17, the animals were tested for EIA (2.5 g/kg, IP) or MIA (10 mg/kg, IP) in the hot plate test. To examine the development of environment-dependent tolerance, animals were injected with ethanol (2.5 g/kg, IP) or an equal volume of saline once a day for 2 days. On day 3, the animals received no treatment. On day 4, the animals were tested for either EIA (25 g/kg, IP) or MIA (10 mg/kg, IP) in the hot plate test. It was found that rats pretreated with ethanol (both self-administration, and IP injections) displayed tolerance to EIA, which was not accompanied by cross- tolerance to MIA.
Bell, R. L., Olson, R. D., & Vaccarino, A. L. (1998). Tolerance to ethanol analgesia is not accompanied by cross-tolerance to morphine analgesia in rats. Pharmacology Biochemistry and Behavior, 59(1), 123–127. https://doi.org/10.1016/S0091-3057(97)00380-8