ROLES OF DOPAMINE-RECEPTORS IN LONG-TERM DEPRESSION - ENHANCEMENT VIAD1 RECEPTORS AND INHIBITION VIA D2 RECEPTORS

The effects of both the activation and the blockade of D1 or D2 dopami ne receptors on long-term depression (LTD) of synaptic transmission, a nd the involvement of NMDA and GABA receptors in LTD, were investigate d in CA1 neurons of rat hippocampal slices. Low-frequency stimulation (LFS, 450 pulses at 1 Hz) produced LTD of the slope of field EPSPs (-1 4.3%, mean, n = 10). The induction of LTD was blocked by the NMDA rece ptor 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 bloc kade of D2 receptors by sulpiride produced significantly larger LTD th an the control LTD (-31.1%, n = 11; -30.6%, n = 9, respectively). Alth ough LTD was blocked by picrotoxin, a GABA(A) receptor/Cl- channel ant agonist (4.9%, n = 8), LTD was produced by LFS in the medium containin g both SKF-38393 and picrotoxin (-27.3%, n = 7). These results indicat e 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 D 2 receptors are involved in the modulation of LTD in that the activati on of D1 receptors enhances LTD, while that of D2 receptors inhibits L TD, and (3) while the induction of LTD is blocked by picrotoxin, this effect is superseded by SKF-38393.