The development of tolerance to the hypothermic effect of ethanol was examined during chronic ethanol treatment (5 g/kg PO daily) at various ambient temperatures (Ta). Tolerance to the hypothermic effect of ethanol, monitored at five-day intervals for 25 days, developed rapidly when ethanol treatment was carried out at 4°C. On the other hand, rats receiving ethanol treatment at a Ta of 36°C, at which they did not experience hypothermia, acquired tolerance more slowly, but achieved the same level of tolerance as other groups after 25 days of treatment. This cannot be accounted for by the repeated testing at 21°C at five-day intervals, since it was also observed under a non-repeated testing condition. Once tolerance to the hypothermic effect of ethanol was acquired, termination of ethanol treatment resulted in the loss of tolerance, but mere prevention of the hypothermic effect of ethanol did not. These results suggest that tolerance still developed even though the organisms did not experience hypothermia during ethanol treatment. Therefore there appears to be a component of tolerance, that depends upon a direct cellular action of the drug, as distinct from the physiological consequences of the action. However, variation in the degree of physiological disturbance (hypothermia) during drug exposure can modulate the rate of development of this tolerance. © 1986.
Le, A. D., Kalant, H., & Khanna, J. M. (1986). Influence of ambient temperature on the development and maintenance of tolerance to ethanol-induced hypothermia. Pharmacology, Biochemistry and Behavior, 25(3), 667–672. https://doi.org/10.1016/0091-3057(86)90157-7