The paraventricular nucleus of the hypothalamus (PVN), is central to integration of the cardiovascular response to psychological stress. Furthermore, GABA_A receptor expressing parvocellular PVN neurones are believed to be fundamentally important to this response. Tachykinins are known modulators of GABA_A receptors [3]. During psychological stress brain tachykinin concentrations increase and have been linked to the resulting tachycardia and increase in blood pressure [2]. Tachykinin receptors may, therefore, offer a useful target for future therapeutic intervention in stress-related heart disease. In a previous study, we reported substance P (SP), a member of the tachykinin family, to inhibit the GABA_A receptor currents of spinally projecting parvocellular neurones [1]. All three tachykinin receptor subtypes (NK1, 2 and 3) are sensitive to SP and have previously been identified in the hypothalamus. Each of these receptors is therefore a potential candidate for the inhibition of GABA_A currents by SP. In this study, we sought to identify the tachykinin receptors involved with modulation of GABA_A receptors of anatomically and morphologically identified parvocellular neurones in the rat PVN. Methods were similar to those described elsewhere [4]; briefly; 14-16 day rats were humanely killed, hypothalami removed to iced artificial cerebrospinal fluid (ACSF) and 250μm sections cut. For whole-cell experiments, neurones were held at -60mV and superfused at 2ml/min with 34-36°C modified ACSF. GABA was applied by pressure ejection. Drugs were added to the superfusing ACSF. Mean data are presented ±S.E.M. GABA (300μM) evoked whole-cell currents in the range of 0.1-5 nA. These reversed near to ECl and were inhibited by bicuculline (10μM, residual current 13±5%, n=5), confirming these to be GABA_A currents. GABA current amplitudes were decreased to 23±10% (n=5, p≤0.005, t test) by SP (1μM). Neither NKA4-10 (1μM), NKB (1μM) nor the selective NK3 agonist senktide (1μM) had a significant effect on GABA currents (75.8±6%, n=7; 92±3%, n=4; and 83±11%, n=8, respectively). In the presence of the NK1/2 antagonist spantide (1μM), SP no longer significantly inhibited GABA currents (119±9%, n=3). In this study, we report the inhibition of GABA currents by SP, but not by the NK3 selective agonists senktide or NKB. These data suggest the involvement of NK1 receptors in the modulation of GABA_A currents by SP.