PMID- 10900234
OWN - NLM
STAT- MEDLINE
DCOM- 20000824
LR  - 20221207
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 294
IP  - 2
DP  - 2000 Aug
TI  - Differential effect of local infusion of serotonin reuptake inhibitors in the 
      raphe versus forebrain and the role of depolarization-induced release in 
      increased extracellular serotonin.
PG  - 571-9
AB  - Systemic administration of selective serotonin reuptake inhibitors (SSRIs) 
      elicits larger increases in serotonin (5-HT) in raphe than in forebrain sites. 
      Because serotonergic neuronal activity is suppressed, the mechanism underlying 
      SSRI-induced increases in extracellular 5-HT is unclear. This study determined 
      whether local infusion of SSRIs also elicited regionally selective increases in 
      extracellular 5-HT, and whether changes depended on serotonergic neuronal 
      depolarization. Conventional microdialysis methods were used to measure 5-HT in 
      dorsal raphe (DRN), median raphe, nucleus accumbens (NAcc), and frontal cortex of 
      unanesthetized rats. During infusion of SSRIs into each site, the maximum 
      response was an approximately 6- to 7-fold increase in 5-HT in NAcc and frontal 
      cortex, and an approximately 20-fold increase in DRN and median raphe. The larger 
      increase in 5-HT in raphe was confirmed using zero-net-flux microdialysis. In 
      NAcc, baseline 5-HT was 0.7 nM, and levels increased to a maximum of 3.1 nM 
      during infusion of the SSRI citalopram. Baseline 5-HT in DRN was greater, 1.3 nM, 
      and increased to 12.4 nM in response to citalopram. Consistent with evidence that 
      autoreceptor activation inhibits serotonergic neuronal discharge, SSRI infusion 
      into DRN produced a moderate decrease in 5-HT in NAcc. However, increases in 5-HT 
      in DRN elicited by SSRI infusion were attenuated by 
      8-hydroxydipropylaminotetralin and tetrodotoxin. These data indicate that 
      depolarization-dependent 5-HT release was not fully inhibited during SSRI 
      infusion into DRN. In summary, SSRIs produce larger increases in extracellular 
      5-HT in raphe than in forebrain sites. Increases depend in part on 
      depolarization-induced release, which may be greater in raphe than in forebrain.
FAU - Tao, R
AU  - Tao R
AD  - Department of Cell Biology and Neuroscience, Nelson Biological Laboratories, 
      Rutgers University, Piscataway, NJ 08854-8082, USA.
FAU - Ma, Z
AU  - Ma Z
FAU - Auerbach, S B
AU  - Auerbach SB
LA  - eng
GR  - MH51080/MH/NIMH NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Receptors, Serotonin, 5-HT1)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0DHU5B8D6V (Citalopram)
RN  - 333DO1RDJY (Serotonin)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology
MH  - Animals
MH  - Citalopram/pharmacology
MH  - Dendritic Cells/drug effects/metabolism/physiology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Extracellular Space/metabolism
MH  - Male
MH  - Microdialysis
MH  - Nucleus Accumbens/drug effects/metabolism/physiology
MH  - Prosencephalon/*drug effects/metabolism/physiology
MH  - Raphe Nuclei/*drug effects/metabolism/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/physiology
MH  - Receptors, Serotonin, 5-HT1
MH  - Serotonin/*metabolism
MH  - Serotonin Receptor Agonists/pharmacology
MH  - Selective Serotonin Reuptake Inhibitors/administration & dosage/*pharmacology
MH  - Tetrodotoxin/pharmacology
EDAT- 2000/07/20 11:00
MHDA- 2000/08/29 11:01
CRDT- 2000/07/20 11:00
PHST- 2000/07/20 11:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/07/20 11:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2000 Aug;294(2):571-9.