Effects of endogenous melatonin on glutamate and GABA rhythms in the striatum of unilateral 6-hydroxydopamine-lesioned rats.

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 neurotransmitters 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 striatal 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-lesioned 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-lesioned 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 rats. 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.