This is a term used to describe a neurobiological phenomenon wherein long-term depolarization of the post-synaptic membrane has occurred, making it insensitive to the transmitter substance.
For example, say one was to administer a drug that blocked dopamine receptors on a given neuron. In experiments, it has been shown that synapse responsible for triggering this neuron will attempt to compensate by firing at an abnormally high rate for about a three week period, after which the firing rate will return to normal. It is suggested that this result occurs because the membranes of the cells "depolarize," (referring to a voltage decrease between the cell membrane and the cytoplasm within the neuron) blocking the neuron's ability to fire and release the neurotransmitter.
Depolarization block at the dopaminergic neurons has been observed with many of the current antipsychotic drugs, and is therefore used as a screening criteria to discover new drugs of this category. It is not known, however, whether or not the depolarization block phenomenon itself is related to the efficacy of the drug.