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Characterization of electroencephalographic and biochemical responses at 5‐ HT promoting drug‐induced onset of serotonin syndrome in rats
Author(s) -
Ma Zhiyuan,
Rudacille Mary,
Prentice Howard M.,
Tao Rui
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12141
Subject(s) - serotonin syndrome , serotonin , clorgyline , 5 ht receptor , electroencephalography , psychology , monoamine oxidase , moclobemide , reuptake , mdma , medicine , pharmacology , endocrinology , chemistry , neuroscience , serotonergic , receptor , antidepressant , biochemistry , hippocampus , enzyme
Many psychotropic substances used either for medications or illicit recreational purposes are able to produce an increase in extracellular serotonin (5 HT ) in the CNS . 5 HT is well known to improve mood; however, only when the levels of its release are in an appropriate range. Excessive 5 HT is harmful, and will generally result in serotonin syndrome. To date, clinical diagnosis of serotonin syndrome relies exclusively on observation of symptoms because of a lack of available laboratory tests. The goal of this study was to characterize the onset of the syndrome using laboratory settings to determine excessive 5 HT ‐evoked neurological abnormalities. Experiments were carried out in rats with the syndrome being elicited by three groups of 5 HT ‐promoting drugs: (i) (±)‐3,4‐methylenedioxymethamphetamine ( MDMA ); (ii) a combination of the monoamine oxidase inhibitor clorgyline with the 5 HT precursor 5‐hydroxytryptophan; (iii) clorgyline combined with the serotonin‐selective reuptake inhibitor paroxetine. The onset of the syndrome was characterized by electroencephalography ( EEG ), tremor, and brain/plasma 5 HT tests. We found that a mild syndrome was associated with reduced EEG amplitudes while a severe syndrome strongly with seizure‐like EEG activity and increased tremor activity. The occurrence of the syndrome was confirmed with microdialysis, showing excessive 5 HT efflux in brain dialysate and the increased concentration of unbound 5 HT in the plasma. Our findings suggest that the syndrome onset can be revealed with EEG recording, measurements of tremor activity and changes of unbound 5 HT concentration in the plasma.