Alcohol tolerance and nicotine cross-tolerance in adolescent mice

The present experiment was designed to evaluate the development of toleranc e to alcohol and cross-tolerance to nicotine in adolescent mice. C57BL/6J m ice (30-40 days old) were injected IP with alcohol (2.5 g/kg) for 4 consecu tive days. A control group received four saline injections. On the test day , all subjects received an alcohol injection. Tolerance to alcohol's hypoth ermic effect was observed. Mice (male and female) exposed to alcohol for th e 4 previous days showed less hypothermic response to an alcohol challenge than animals injected for 4 days with saline and then challenged with alcoh ol. Tolerance to alcohol's motor in coordinating effects and differences in blood alcohol concentrations were not observed. Thirty days following alco hol treatment, the same mice received a single nicotine injection (1 mg/kg) to assess cross-tolerance. Nicotine's effect on locomotor activity (open f ield test) and rectal temperature varied as a function of prior adolescent alcohol exposure and gender. Specifically, female mice who had been exposed to alcohol administrations were more resistant to nicotine's effect on loc omotion and temperature than saline-treated animals. In summary, these data demonstrate that adolescent mice develop tolerance to some, but not all, a lcohol-induced responses, and that female mice are cross-tolerant to nicoti ne's effects on temperature and activity.