Effect of L-prolyl-L-leucyl-glycinamide (PLG) on neuroleptic-induced catalepsy and dopamine/neuroleptic receptor bindings.

The mechanism of action subserving the potential anti-Parkinsonian properties of L-prolyl-L-leucyl-glycinamide (PLG) was investigated in behavioural and neurochemical models of dopaminergic function in the rat. Acute administration of PLG (20 and 40 mg kg-1 SC) failed to alter appreciably the intensity of the cataleptic response elicited by haloperidol (3 mg kg-1 IP). By contrast, chronic PLG treatment (20, 40 and 80 mg kg-1 SC twice daily for five days) significantly attenuated haloperidol-induced catalepsy. The effect of PLG on in vitro dopamine/neuroleptic receptor binding in rat striatum as differentially labelled by apomorphine and spiroperidol was also examined. PLG selectively enhanced the affinity of the specific binding of agonist [3H] apomorphine to dopamine receptors in the striatum, but had no effect on [3H] spiroperidol binding. The behavioural and biochemical results obtained in the present study raise the possibility that PLG may facilitate nigro-striatal dopaminergic neurotransmission through interacting with a unique PLG receptor functionally coupled to the dopamine receptor-adenylate cyclase complex.