Taurine is one of the most abundant free amino acids in the mammalian brain, and acts as an inhibitory neurotransmitter or neuromodulator in the CNS (Huxtable, 1989; Kuriyama & Hashimoto, 1998). Taurine deficiency has been confirmed in many neuropathological conditions (Perry, 1976). In previous studies, it has been demonstrated that both local and systemic administration of NMDA caused a significant increase in taurine levels in the rat hippocampus and striatum (Shibanoki et al., 1993). In the present study, we have further investigated the effects of local administration of NMDA on taurine levels in the rat frontal cortex and striatum using in vivo microdialysis.

Male rats (Wistar, 250 - 300 g, Harlan) were anaesthetised using 3% isoflurane/95% oxygen. Guide cannulae were stereotaxically inserted and fixed by dental cement. Rats were allowed at least a week for recovery during which time post-operative analgesia was administered once per day for up to 3 days. A microdialysis probe (4 mm membrane) was inserted into the frontal cortex (position of probe tip relative to Bregma (Paxinos & Watson, 1986) mm: A +3.5, L -1.5, V -5.5,) or striatum (mm, A -0.8, L -3.0, V -4.5) and perfused with artificial cerebrospinal fluid (aCSF) at 2 µl/min 18 hr before the experiments commenced. Dialysate amino acid levels were analysed by HPLC coupled with fluorescence detection.

The basal levels of taurine were 0.78 ± 0.08 and 1.02 ± 0.12 µM in the rat frontal cortex and striatum respectively. In the rat frontal cortex, local administration of NMDA (100 and 500 µM, via the microdialysis probe) significantly increased taurine levels (n=5-6, P<0.05, Student’s t test vs basal), above basal (defined as mean of 3 samples prior to drug administration). In the rat striatum, NMDA
(50 - 500 µM) significantly enhanced the taurine levels (n=5, P<0.05) above basal. 60 min pre-treatment with MK801 (0.15 mg/kg, i.p) significantly reduced the NMDA (100 µM)-induced enhancement of taurine levels in the striatum ( n=6, P<0.05, Student’s t test vs NMDA 100 µM), whilst MK801 (0.15 mg/kg, ip.) alone had no effect (Table 1).

Table 1. Effect of local administration of NMDA and combination with MK801 on taurine levels in the rat frontal cortex and striatum

The present study demonstrated that local administration of NMDA significantly increased taurine levels in a concentration dependent manner in both rat frontal cortex and striatum. Such results are in agreement with previous findings (Shibanoki et al., 1993). The increased taurine levels induced by NMDA were significantly reduced by pre-treatment with the non-competitive NMDA receptor antagonist MK801, indicating that the NMDA-induced response was directly NMDA receptor mediated. The physiological and pharmacological functions of taurine are poorly understood though it has been reported that it may act as an inhibitory neurotransmitter or modulator of GABAergic function (Huxtable, 1989; Kuriyama et al., 1998) and may interact with a specific taurine receptor (Wu et al., 1987) to exert its biological activity.

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