Striatal dopamine D1 receptors have been shown to inhibit NMDA currents without G-protein activation (Lee et al. 2002; Tong & Gibb, 2004). We hypothesise that this inhibition may be mediated by a change in NMDA receptor (NMDAR) trafficking. The non-receptor tyrosine kinase, Src, has been shown to be involved in NMDAR internalization (Dunah & Standaert, 2004) and in this study we tested the effect of a potent Src family-selective tyrosine kinase inhibitor (PP2) on D1 modulation of NMDARs. Dynamin also plays an essential role in clathrin mediated receptor endocytosis and we therefore also tested the effect of a dynamin inhibitory peptide (Kittler et al. 2000) on D1 inhibition of NMDA responses. In striatal slices from 7-day-old rats, responses to 0.01 mM NMDA and 0.01 mM glycine in the presence of TTX (100 nM) were recorded with ATP (1 mM) and GTP (1 mM) in the pipette solution. In the presence of intracellular PP2 (10 µM), D1 inhibition of the NMDA current was significantly reduced from 38 ± 12% (n = 10 cells) to 1 ± 8.2% (n = 9 cells, unpaired t test, P<0.05) suggesting non-receptor Src tyrosine kinase activation is involved in D1 receptor inhibition of NMDA responses. Intracellular dynamin inhibitory peptide (QVPSRPNRAP, 0.05 mM) significantly attenuated the D1 inhibition to 3.08 ± 8.15% (n = 9 cells, unpaired t test, P<0.05). These results suggest dynamin-dependent endocytosis is important in D1 inhibition of NMDA responses.