We have previously reported a time-dependent increase in melatonin (MLT) and decrease In dopamine (DA) in striatal dialysate 3 weeks after unilateral 6-hydroxydopamine (6-OHDA) lesioning In the rat substantia nigra pars compacta (SNc) and medial forebrain bundle (MFB).This study aimed to investigate dynamic and circadian variations in DA,MLT,glutamate (Glu) and γ-aminobutyric acid (GABA) in striatal dialysates in the same 6-OHDA animal model.These neurotransmittere were determined using high.performance liquid chromatography (HPLC).Three weeks following 6-OHDA lesioning,there was a significant increase in extracellular Glu (156%) and decrease in GABA (15%) and DA (85%) in the lesioned striatum.These changes continued over time.Concomitantly,MLT was increased by 107% in the lesioned striatel dialysates after 4 weeks,and continued to increase gradually over time.Six weeks post-treatment,levels of MLT secretion at 12 time points were higher,and the peak time of MLT secretion was earlier,in 6-OHDA-lesloned rats compared with vehicle-treated rats.In addition,significant variations in extracellular levels of Glu and GABA between day and night were observed in vehicle-treated rat striatum.However,no circadian variations were observed In the striatum of unilateral 6-OHDA-iesloned rats.Six weeks post-treatment,MLT levels correlated well with Glu and GABA levels at corresponding time-points in the striatum ipsilateral to the injected side in both groups,and increased MLT levels also correlated well with changes in Glu and GABA in the striatum In 6-OHDA-lesioned rate.These data suggest that 6-OHDA lesioning affects the endogenous productions of DA,MLT,Glu and GABA,and changes the MLT secretion pattern.Augmented striatal MLT levels and advanced MLT secretion pattern caused by unilateral intracerebral injection of 6-OHDA may influence the variations in Glu and GABA between day and night.