PMID- 19845681
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 158
IP  - 6
DP  - 2009 Nov
TI  - Further pharmacological characterization of 5-HT(2C) receptor agonist-induced 
      inhibition of 5-HT neuronal activity in the dorsal raphe nucleus in vivo.
PG  - 1477-85
LID - 10.1111/j.1476-5381.2009.00406.x [doi]
AB  - BACKGROUND AND PURPOSE: Recent experiments using non-selective 
      5-hydroxytryptamine (5-HT)(2C) receptor agonists including WAY 161503 suggested 
      that midbrain 5-HT neurones are under the inhibitory control of 5-HT(2C) 
      receptors, acting via neighbouring gamma-aminobutyric acid (GABA) neurones. The 
      present study extended this pharmacological characterization by comparing the 
      actions of WAY 161503 with the 5-HT(2C) receptor agonists, Ro 60-0275 and 
      1-(3-chlorophenyl) piperazine (mCPP), as well as the non-selective 5-HT agonist 
      lysergic acid diethylamide (LSD) and the 5-HT releasing agent 
      3,4-methylenedioxymethamphetamine (MDMA). EXPERIMENTAL APPROACH: 5-HT neuronal 
      activity was measured in the dorsal raphe nucleus (DRN) using extracellular 
      recordings in anaesthetized rats. The activity of DRN GABA neurones was assessed 
      using double-label immunohistochemical measurements of Fos and glutamate 
      decarboxylase (GAD). KEY RESULTS: Ro 60-0175, like WAY 161503, inhibited 5-HT 
      neurone firing, and the 5-HT(2C) antagonist SB 242084 reversed this effect. mCPP 
      also inhibited 5-HT neurone firing ( approximately 60% neurones) in a SB 
      242084-reversible manner. LSD inhibited 5-HT neurone firing; however, this effect 
      was not altered by either SB 242084 or the 5-HT(2A/C) receptor antagonist 
      ritanserin but was reversed by the 5-HT(1A) receptor antagonist WAY 100635. 
      Similarly, MDMA inhibited 5-HT neurone firing in a manner reversible by WAY 
      100635, but not SB 242084 or ritanserin. Finally, both Ro 60-0275 and mCPP, like 
      WAY 161503, increased Fos expression in GAD-positive DRN neurones. CONCLUSIONS 
      AND IMPLICATIONS: These data strengthen the hypothesis that midbrain 5-HT 
      neurones are under the inhibitory control of 5-HT(2C) receptors, and suggest that 
      the 5-HT(2C) agonists Ro 60-0175, mCPP and WAY 161503, but not LSD or MDMA, are 
      useful probes of the mechanism(s) involved.
FAU - Queree, P
AU  - Queree P
AD  - University Department of Pharmacology, Oxford, UK.
FAU - Peters, S
AU  - Peters S
FAU - Sharp, T
AU  - Sharp T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091020
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Pyrazines)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptor, Serotonin, 5-HT2C)
RN  - 0 (Serotonin 5-HT2 Receptor Agonists)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 333DO1RDJY (Serotonin)
RN  - EC 4.1.1.15 (Glutamate Decarboxylase)
SB  - IM
MH  - Animals
MH  - Glutamate Decarboxylase/metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Proto-Oncogene Proteins c-fos/drug effects/genetics
MH  - Pyrazines/pharmacology
MH  - Quinoxalines/pharmacology
MH  - Raphe Nuclei/*drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Serotonin, 5-HT2C/metabolism
MH  - Serotonin/*metabolism
MH  - *Serotonin 5-HT2 Receptor Agonists
MH  - Serotonin Receptor Agonists/*pharmacology
PMC - PMC2795214
EDAT- 2009/10/23 06:00
MHDA- 2010/02/26 06:00
PMCR- 2010/11/01
CRDT- 2009/10/23 06:00
PHST- 2009/10/23 06:00 [entrez]
PHST- 2009/10/23 06:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
PHST- 2010/11/01 00:00 [pmc-release]
AID - BPH406 [pii]
AID - 10.1111/j.1476-5381.2009.00406.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2009 Nov;158(6):1477-85. doi: 10.1111/j.1476-5381.2009.00406.x. 
      Epub 2009 Oct 20.