Although functional glycine receptors (GlyRs) are present in the mature nucleus accumbens (NAcc) (Martin and Siggins 2002), an important area of the mesolimbic dopamine system involved in drug addiction, their role has been unclear because the NAcc contains little glycine. However, taurine, an agonist of GlyRs is abundant throughout the brain, especially during early development. In the present study on freshly dissociated NAcc neurons from young Sprague-Dawley rats (12-21-day-old), we found that both glycine and taurine can strongly depolarize NAcc neurons and modulate their excitability. In voltage-clamped NAcc neurons, glycine and taurine elicited chloride currents (I_Gly and I_Tau) with an EC₅₀ of 0.12 and 1.25 mM, respectively. The reversal potential of I_Gly or I_Tau was 0 mV in conventional whole-cell mode and -30 mV in gramicidin-perforated mode. At concentrations <1 mM, both glycine and taurine were very effectively antagonized by strychnine and by picrotoxin (with an IC₅₀ of 60 nM and 36.5 µM for I_Gly, and 40 nM and 42.2 µM for I_Tau) but were insensitive to bicuculline 10 µM). The currents elicited by taurine (1 mM) showed complete cross-desensitization with I_Gly, but none with -aminobutyric acid (GABA)-induced currents (IGABA). However, ITau elicited by very concentrated taurine (10 mM) showed partial cross-desensitization with I_GABA, and it was substantially antagonized by 10 µM bicuculline. These results indicate that taurine binds mainly to GlyRs in NAcc, but it could be a partial agonist of GABA_A receptors. By activating GlyRs, taurine may play an important physiological role in the control of NAcc function, especially during development.