Time interval between sequential exposures to ethanol is critical for the development of neural tolerance or sensitivity.

DBA/2 and SW mice were injected sequentially with 4 g/kg body weight of ethanol five times at 24-, 48- and 72-h intervals, and the sleeping time induced by each exposure was recorded. DBA/2 mice given ethanol at 24-h and 48-h intervals developed tolerance, i.e., slept less than previously untreated animals, whereas SW mice slept longer, i.e., developed an increased neural sensitivity to ethanol. Injection of ethanol at 72-h intervals did not change the duration of sleep in either mouse strain. These data show the importance of timing of sequential ethanol injections for the induction of both tolerance and increased neural sensitivity.