PMID- 15499608
OWN - NLM
STAT- MEDLINE
DCOM- 20050217
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 55
IP  - 1
DP  - 2005 Jan
TI  - Distinct modulatory roles of sigma receptor subtypes on glutamatergic responses 
      in the dorsal hippocampus.
PG  - 37-44
AB  - Sigma ligands have been previously shown to modulate the N-methyl-D-aspartate 
      (NMDA) response in the dorsal hippocampus, such that low doses of sigma agonists 
      dose-dependently potentiate the response. Recent studies with the sigma ligand 
      4-IBP found it to act differently from the sigma ligands (+)-pentazocine and DTG 
      in the modulation of 5-HT firing activity in the dorsal raphe nucleus (DRN), as 
      its effects were not blocked by the sigma antagonists which reversed those of 
      (+)-pentazocine or DTG. Thus, this study set out to characterize 4-IBP's action 
      at sigma receptors using the hippocampal paradigm of sigma ligand activity. 
      Interestingly, we found that in 50% of the neurons recorded, 4-IBP (20 microg/kg 
      i.v.) produced a potentiation of both NMDA- and quisqualate (QUIS)-induced 
      responses. In the other 50% of neurons, 4-IBP produced an attenuation of both 
      QUIS and NMDA responses. The sigma1 antagonist NE-100 blocked the reduction 
      induced by 4-IBP, while the nonselective sigma antagonist haloperidol blocked all 
      responses induced by 4-IBP. These data suggest that, in this model, 4-IBP may be 
      acting as an agonist or inverse agonist of sigma receptors. Furthermore, the 
      initial responses to NMDA and QUIS were higher in the group in which 4-IBP 
      induced an attenuation of the firing activity. This suggests a modulatory role 
      for 4-IBP on glutamatergic neurotransmission in the hippocampus, which appears to 
      involve two distinct pathways, mediated by different sigma1 receptor subtypes, an 
      NE-100 and haloperidol-sensitive sigma1 receptor, and an NE-100-insensitive, 
      haloperidol-sensitive sigma1 receptor. This modulatory role has implications for 
      disorders that involve glutamatergic transmission in the hippocampus.
CI  - copyright (c) 2004 Wiley-Liss, Inc.
FAU - Bermack, Jordanna E
AU  - Bermack JE
AD  - Department of Psychiatry, McGill University, Montreal, Quebec, Canada H3A 1A1.
FAU - Debonnel, Guy
AU  - Debonnel G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Anisoles)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Piperidines)
RN  - 0 (Propylamines)
RN  - 0 (Receptors, sigma)
RN  - 149409-57-4 (N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine 
      monohydrochloride)
RN  - 155798-12-2 (N-(N-benzylpiperidin-4-yl)-4-iodobenzamide)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 8OC22C1B99 (Quisqualic Acid)
SB  - IM
MH  - Action Potentials/drug effects/physiology
MH  - Analysis of Variance
MH  - Animals
MH  - Anisoles/pharmacology
MH  - Antipsychotic Agents/pharmacology
MH  - Benzamides/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Glutamic Acid/*metabolism
MH  - Hippocampus/anatomy & histology/drug effects/*metabolism
MH  - Male
MH  - N-Methylaspartate/pharmacology
MH  - Piperidines/*pharmacology
MH  - Propylamines/pharmacology
MH  - Quisqualic Acid/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, sigma/agonists/antagonists & inhibitors/*physiology
EDAT- 2004/10/23 09:00
MHDA- 2005/02/18 09:00
CRDT- 2004/10/23 09:00
PHST- 2004/10/23 09:00 [pubmed]
PHST- 2005/02/18 09:00 [medline]
PHST- 2004/10/23 09:00 [entrez]
AID - 10.1002/syn.20085 [doi]
PST - ppublish
SO  - Synapse. 2005 Jan;55(1):37-44. doi: 10.1002/syn.20085.