Stimulation is necessary for the development of tolerance to a neuronal effect of ethanol.

Ethanol accelerates the decay of post-tetanic potentiation at an identified synapse in Aplysia. We have previously shown that with repeated exposures the ethanol effect diminishes, a development termed "tolerance." Here we present evidence that the establishment of tolerance depends on a adequate stimulation of the presynaptic terminal in the presence of ethanol. Elevated magnesium in the perfusion medium prevents tolerance, whereas elevated calcium in the perfusion medium reduces the amount of stimulation required for tolerance to develop.