Regional, reversible ultrastructural changes in rat brain with chronic neuroleptic treatment

Administration of the dopamine receptor antagonist (neuroleptic, antipsychotic), haloperidol, resulting in an increase in the number of dopamine binding sites in the striatum and nucleus accumbens, has been well established. These increases disappear following withdrawal of treatment. Ultrastructurally, we found an increase in the number of synapses containing perforated postsynaptic densities (PSDs) following haloperidol administration within the caudate nucleus but not within the nucleus accumbens. The effect in the caudate reversed following cessation of treatment. We speculate that the terminals undergoing the change are not dopaminergic but may originate from the cerebral cortex. This reversible morphological increase associated with dopamine antagonist drug therapy may be reflective of the tolerance developed to neuroleptic drug-induced extrapyramidal syndromes and/or may be associated with abnormal motor movements of tardive dyskinesia that occur following long-term treatment.