Accumulating evidence suggests that sensorineural hearing loss in animals is rapidly followed by degenerative changes in central auditory neurons. For example, cochlear removal in birds and mammals results in a reduction in central auditory neuron cell size within 48 hours. A similar decrease in cell size after pharmacologic blockade of auditory nerve electrical activity with tetrodotoxin has been reported. In the present study, we evaluate the reversibility of central auditory changes after a profound sensorineural hearing loss caused by blockade of auditory nerve actions potentials. Tetrodotoxin, which blocks voltage-sensitive sodium channels, was embedded in a slow-release vehicle and placed next to the round window membrane of gerbils. Tetrodotoxin diffused into perilymph and unilaterally blocked electrical activity in auditory nerve axons. Electrical activity blockade was confirmed with recordings of auditory brainstem response. Animals were killed immediately after 24 hours of electrical blockade or 7 days after a transient 24- or 48-hour blockade. Large spherical cells of the anteroventral cochlear nucleus ipsilateral to manipulation were measured and compared to large spherical cells on the opposite, unmanipulated side of the brain. Animals killed immediately after a 24-hour blockade of electrical activity showed a mean decrease of 16% in cell size ipsilateral to the blockade (p less than 0.05). In animals allowed to recover for 7 days after blockade for 24 or 48 hours, cell size returned to previous levels. There was no longer a consistent difference in cell size between the two sides of the brain in these animals (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)