d-Lysergic acid diethylamide differentially affects the dual actions of 5-hydroxytryptamine on cortical neurons.

5-Hydroxytryptamine (5-HT; 10(-4) M) produces an initial depolarization, followed by a long-lasting hyperpolarization, when focally applied to pyramidal neurons in the somatosensory cortex of the rat. Application of the selective 5-HT1A agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT; 10(-6) M) or d-lysergic acid diethylamide (d-LSD; 10(-6) M), produced only a hyperpolarizing response which was larger than the response to 5-HT. Application of 8-OH-DPAT (10(-6) M) and 5-HT (10(-4) M) together produced an initial depolarizing response, similar to the response with 5-HT alone, followed by a hyperpolarizing response which was 23 +/- 3% larger than with 5-HT alone. By contrast, the application of d-LSD (10(-6) M) and 5-HT (10(-4) M) together produced either no depolarization (7 of 13 cells) or a significantly smaller depolarizing response (36 +/- 4% of the response to 5-HT alone), as well as a hyperpolarizing response which was 33 +/- 4% larger than with 5-HT alone. Therefore, d-LSD displayed a unique pharmacological ability to both mimic and block the effect of 5-HT on single neurons in somatosensory cortex of the rat.