A comparative electrophysiological and biochemical assessment of serotonin (5-HT) and a novel 5-HT agonist (MK-212) on central serotonergic receptors.

The inhibitory effects of microiontophoretically-applied serotonin (5-HT) and 6-chloro-2[1-piperazinyl]pyrazine (MK-212) were examined on spontaneously firing somatosensory cerebral cortical neurons and dorsal raphe neurons in rats anesthetized with chloral hydrate. On cortical neurons, MK-212 caused only weak and variable inhibition of extracellularly recorded neuronal activity, compared to the effects of 5-HT. However, on raphe cells, MK-212 exerted potent inhibitory effects, equivalent to those observed with 5-HT. In contrast to the inhibitory actions of D-lysergic acid diethylamide (LSD) and 5-HT at presumed 5-HT autoreceptors, MK-212 did not affect the in vitro release of [3H]5-HT from slices of rat hypothalamus stimulated by methiothepin. These findings, coupled with previously reported behavioral, biochemical and electrophysiological effects of MK-212 may indicate that this novel serotonergic agonist uniquely discriminates between subsets of serotonergic receptors in the CNS.