PMID- 23286698
OWN - NLM
STAT- MEDLINE
DCOM- 20130719
LR  - 20211021
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 125
IP  - 5
DP  - 2013 Jun
TI  - Characterization of electroencephalographic and biochemical responses at 5-HT 
      promoting drug-induced onset of serotonin syndrome in rats.
PG  - 774-89
LID - 10.1111/jnc.12141 [doi]
AB  - Many psychotropic substances used either for medications or illicit recreational 
      purposes are able to produce an increase in extracellular serotonin (5HT) in the 
      CNS. 5HT is well known to improve mood; however, only when the levels of its 
      release are in an appropriate range. Excessive 5HT 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 5HT-evoked neurological 
      abnormalities. Experiments were carried out in rats with the syndrome being 
      elicited by three groups of 5HT-promoting drugs: (i) 
      (+/-)-3,4-methylenedioxymethamphetamine (MDMA); (ii) a combination of the monoamine 
      oxidase inhibitor clorgyline with the 5HT 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 5HT 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 5HT efflux in brain dialysate and 
      the increased concentration of unbound 5HT in the plasma. Our findings suggest 
      that the syndrome onset can be revealed with EEG recording, measurements of 
      tremor activity and changes of unbound 5HT concentration in the plasma.
CI  - (c) 2013 International Society for Neurochemistry.
FAU - Ma, Zhiyuan
AU  - Ma Z
AD  - Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, 
      Florida 33431, USA.
FAU - Rudacille, Mary
AU  - Rudacille M
FAU - Prentice, Howard M
AU  - Prentice HM
FAU - Tao, Rui
AU  - Tao R
LA  - eng
GR  - R15 DA029863/DA/NIDA NIH HHS/United States
GR  - R15DA029863/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130128
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Serotonin Agents)
RN  - 333DO1RDJY (Serotonin)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism
MH  - Brain Chemistry/drug effects/physiology
MH  - Electroencephalography/*drug effects/methods
MH  - Extracellular Fluid/drug effects/metabolism
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/*metabolism
MH  - Serotonin Agents/*toxicity
MH  - Serotonin Syndrome/chemically induced/*metabolism/*physiopathology
PMC - PMC4242192
MID - NIHMS432864
COIS- Conflicts of interest: The authors declare no conflicts of interest.
EDAT- 2013/01/05 06:00
MHDA- 2013/07/20 06:00
PMCR- 2014/11/24
CRDT- 2013/01/05 06:00
PHST- 2012/07/24 00:00 [received]
PHST- 2012/12/20 00:00 [revised]
PHST- 2013/01/02 00:00 [accepted]
PHST- 2013/01/05 06:00 [entrez]
PHST- 2013/01/05 06:00 [pubmed]
PHST- 2013/07/20 06:00 [medline]
PHST- 2014/11/24 00:00 [pmc-release]
AID - 10.1111/jnc.12141 [doi]
PST - ppublish
SO  - J Neurochem. 2013 Jun;125(5):774-89. doi: 10.1111/jnc.12141. Epub 2013 Jan 28.