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.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*
D011719:Pyrazines; D011985:Receptors, Serotonin; D012701:Serotonin; D008719:Methiothepin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D011189:Potassium Chloride; D008238:Lysergic Acid Diethylamide