Dopaminergic supersensitivity after neuroleptics: time-course and specificity

Area of Science:

• Neuroscience
• Pharmacology
• Clinical Neurology

Background:

• Neuroleptic medications can induce dopaminergic supersensitivity in animal models after a single dose.
• The clinical manifestation of tardive dyskinesia (TD) typically requires prolonged neuroleptic exposure over months or years.

Purpose of the Study:

• To reconcile the discrepancy between rapid induction of dopaminergic supersensitivity and the slow development of tardive dyskinesia.
• To propose a model explaining the clinical presentation of TD in relation to dopaminergic supersensitivity.

Main Methods:

• Review of existing literature on neuroleptic-induced dopaminergic supersensitivity and tardive dyskinesia.
• Conceptual framework based on compensatory and decompensatory phases of dopaminergic supersensitivity.

Main Results:

• Subclinical or latent tardive dyskinesia may be compensated in patients undergoing neuroleptic treatment.
• Full-blown tardive dyskinesia might represent a decompensated state of underlying dopaminergic supersensitivity.
• Dopaminergic supersensitivity duration is proposed to be proportional to the length of neuroleptic treatment.

Conclusions:

• The proposed compensatory and decompensatory phases may explain the variable clinical onset and severity of tardive dyskinesia.
• The persistence of tardive dyskinesia after neuroleptic cessation could be related to the prolonged duration of induced dopaminergic supersensitivity.