Melatonin disrupts circadian rhythms of glutamate and GABA in the neostriatum of the awake rat: a microdialysis study

The purpose of this study was to investigate possible circadian changes in extracellular concentrations of glutamate (GLU) and gamma -aminobutyric aci d (GABA), and the influence of melatonin on the levels of these neurotransm itters in the neostriatum of awake rats using in vivo microdialysis. At the same time, the concentrations of the amino acids taurine (TAU), glutamine (GLN) and arginine (ARG), as well as dopamine (DA) and its metabolites 3, 4 -dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA), were meas ured in the extracellular fluid. When dialysates were collected over a 24-h r period (6 hr dark, 12 hr light, 6 hr dark), both GLU and GABA, without th e infusion of melatonin, exhibited statistically significant rhythms, with higher levels of these constituents during the dark and lower levels during the day. Perfusion with melatonin (for 19 consecutive hours) prevented the daytime reductions in both GLU and GABA. Of the amino acids measured in th e dialysates collected from the neostriatum of non-perfused rats, only ARG exhibited a significant change during the light:dark cycle; again, lowest c oncentrations were measured during the day. While melatonin perfusion did n ot statistically significantly influence neostriatal levels of TAU and ARG, GLN levels continued to drop during the infusion of the indoleamine. Dialy sate concentrations of DA, DOPAC and HVA exhibited circadian rhythms which were not influenced by melatonin perfusion. The findings indicate there are differential effects of melatonin on extracellular neurotransmitter concen trations in the neostriatum of the awake rat. The results also suggest that the day:night variations in GLU and GABA may relate to daily changes in en dogenous melatonin production, while DA and its metabolites are minimally i nfluenced by this secretory product.