The nucleus tractus solitarii (NTS) is the first central site of integration for the arterial baroreceptor reflex. The baroreflex exerts a reciprocal modulation of the sympathetic and parasympathetic nervous systems. Previous work in our laboratory has found differences in the receptor pharmacology for baroreflex modulation of these two outflows within the NTS (Pickering et al. 2003). Since glutamate is likely to be the primary neurotransmitter of baroafferents in the NTS (Talman et al. 1980) we have aimed to determine the role of metabotropic glutamate receptors (mGluR) in the baroreflex arc at the level of the NTS. Studies used the working heart brainstem preparation (Paton, 1996). Wistar rats (65-75g) were decerebrated under deep halothane anaesthesia, bisected sub-diaphragmatically. Preparations were perfused via the aorta with a carbogenated Ringer solution (+ficoll 1.25%, 32°C). Flow through the preparation was computer controlled with a peristaltic pump and used to alter baseline pressure. Baroreceptors were activated with pressure pulses/ramps. Peripheral chemoreceptors were stimulated with NaCN (i.a.). Recordings were made of arterial pressure, heart rate, phrenic nerve and thoracic sympathetic chain (T8-12) activity. Bilateral microinjections (80nl) of drug were made stereotaxically into the NTS at the site of termination of baroafferents. All values are mean±S.E.M. and paired t tests were used. The broad-spectrum mGluR antagonist MCPG produced a dose-dependent (1-50μM), reversible inhibition of the baroreflex bradycardia by up to 81±3% (50μM, p<0.001, n=5). In contrast, MCPG did not affect the baroreflex sympathoinhibition or chemoreflex sympathoexcitation and bradycardia. The group II mGluR selective antagonists LY341495 (100μM) and EGLU (1mM) also reversibly inhibited the baroreflex cardiac gain by 75±5% (p<0.001, n=6) and 68±6.5% (p<0.001, n=5), respectively. None of the mGluR antagonists significantly affected baseline pressure, heart rate, phrenic or sympathetic nerve activity. The inhibition of the baroreflex cardiac gain by LY341495 was reversibly reduced by pre-injecting bicuculline (10μM, n=3) bilaterally into the same site of the NTS. These results suggest that group II mGluRs play a specific role in modulating the cardiac baroreflex. Since group II mGluRs are thought to act as inhibitory autoreceptors to decrease glutamate release it is paradoxical that group II mGluR antagonists should attenuate the cardiac baroreflex. However, the finding that bicuculline prevents this attenuation suggests that group II mGluRs may be located on a circuit involving inhibitory GABA interneurones within the NTS.