Roles of dopamine receptors in long-term depression: Enhancement via D1 receptors and inhibition via D2 receptors

The effects of both the activation and the blockade of D1 or D2 dopamine receptors on long-term depression (LTD) of synaptic transmission, and the involvement of NMDA and GABA receptors in LTD, were investigated in CA1 neurons of rat hippocampal slices. Low-frequency stimulation (LFS, 450 pulses at 1 Hz) produced LTD of the slope of field EPSPs (-14.3%, mean, n = 10). The induction of LTD was blocked by the NMDA receptor antagonist, AP5 (1.4%, n = 7), by the D1 receptor antagonist, SCH-23390 (3.5%, n = 8), or by the D2 receptor agonist, LY-171555 (4.4%, n = 8). Either the activation of D1 receptors by SKF-38393 or the blockade of D2 receptors by sulpiride produced significantly larger LTD than the control LTD (-31.1%, n = 11; -30.6%, n = 9, respectively). Although LTD was blocked by picrotoxin, a GABA(A) receptor/Cl- channel antagonist (4.9%, n = 8), LTD was produced by LFS in the medium containing both SKF-38393 and picrotoxin (-27.3%, n = 7). These results indicate that: (1) the induction of LTD by LFS in hippocampal CA1 neurons is under the influence of both NMDA and GABA receptors; (2) both D1 and D2 receptors are involved in the modulation of LTD in that the activation of D1 receptors enhances LTD, while that of D2 receptors inhibits LTD, and (3) while the induction of LTD is blocked by picrotoxin, this effect is superseded by SKF-38393.