Neuroleptic Drug-Induced Dopamine Receptor Supersensitivity: Antagonism by L-Prolyl-L-Leucyl-Glycinamide

An animal model of tardive dyskinesia was used to evaluate the potential antidyskinetic properties of the neuropeptide L-prolyl-L-leucyl-glycinamide (PLG). In rats, PLG administered concurrently with the neuroleptic drug haloperidol or chlorpromazine antagonized the enhancement of specific [3H]spiroperidol binding in the striatum that is associated with long-term neuroleptic treatment. The results are discussed in relation to a possible functional coupling of the putative PLG receptor with neuroleptic-dopamine receptor complex and clinical implications for tardive dyskinesia.