The purpose of the present study was to determine whether the activation of NPY 
receptors alters catecholamines (CA) synthesis in the central nervous system 
and, if so, to identify the NPY receptor subtype(s) mediating this effect. 
Tyrosine hydroxylation, the rate-limiting step in CA synthesis, was assessed by 
measuring the accumulation of 3,4-dihydroxyphenyalanine (DOPA) by high pressure 
liquid chromatography coupled to electrochemical detection (HPLC-EC) in rat 
striatal dices following incubation of the tissue with the aromatic L-amino acid 
decarboxylase inhibitor m-hydroxybenzyl hydrazine (NSD 1015). Treatment with NSD 
1015 resulted in an increase in DOPA accumulation that was increased even 
further following depolarization with a high potassium (KCl) buffer. PYY13-36 
and NPY13-36 both produced a significant enhancement of the KCl-induced increase 
in DOPA accumulation. The effect of PYY13-36 was completely attenuated by the 
selective Y2 antagonist BIIE0246 suggesting that activation of Y2 receptors 
enhanced the synthesis of dopamine. In contrast to the effects of NPY13-36 and 
PYY13-36; NPY, PYY and PYY3-36 all produced a significant attenuation of the 
KCl-induced increase in DOPA accumulation. The Y1 antagonist BIBO3304 and the 
Y5-antagonist CGP71683A, both prevented the inhibitory effect of NPY converting 
it to a stimulatory effect. The enhancement of the NPY induced increase in DOPA 
accumulation observed by BIBO3304 was attenuated when examined in the presence 
of the Y2 antagonist BIIE0246. These results suggest that activation of NPY 
receptors can modulate the synthesis of CA in the rat striatum. The Y1 and Y5 
receptor appear to be involved in attenuation, while Y2 receptors are involved 
in the stimulation of synthesis.