Neuroscience 2002 Abstract
| Presentation Number: | 490.12 |
|---|---|
| Abstract Title: | Inhibition of the anoxic depolarization by the sigma receptor (σR) ligand haloperidol. |
| Authors: |
Jarvis, C. R.*1
; Biedermann, A. J.1
; Andrew, R. D.1
1Dept Anat & Cell Biol, Queen's Univ, Kingston, Canada |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Ischemia -- Neuroprotection and tolerance |
| Session: |
490. Ischemia: neuroprotection and mechanisms VI Poster |
| Presentation Time: | Tuesday, November 5, 2002 11:00 AM-12:00 PM |
| Location: | Hall A2-B3 W-27 |
| Keywords: | NEOCORTEX, NEUROPROTECTION, OPTICAL IMAGING, ISCHEMIA |
In response to severe ischemia, neurons undergo anoxic depolarization (AD), a spreading signal that propagates at 1-3 mm/min through gray matter. We have reported blockade of AD by certain σ1R ligands (SFN Abstr., 26:282.15, 2001). Here we tested haloperidol (HAL), a σR ligand and antispychotic, for its ability to block AD. We imaged cell swelling at the AD front in rat neocortical slices at 35°C. AD was evoked by 5 min bath application of 100 µM ouabain which simulates ischemia. AD was imaged as a propagating front of elevated light transmittance, arising 288 ± 90.1 sec following ouabain exposure (n=26/26 slices). Pretreatment with 30, 50 and 100 (but not 10) µM HAL blocked AD in 34 of 41 slices. Sulpiride (100 µM, 12/12) or AP-5 (50 µM, 8/8) did not block or delay AD. Moreover, cell swelling evoked by 50 µM NMDA (10/10) persisted with 50 µM HAL (14/14). Thus, HAL effects are not through antagonism of D2 or NMDA receptors but possibly through σ2R agonism. However, AD block by 50 µM HAL was not reversed by the σ2R antagonist SM-21 (100 µM, 7/8) or the σR acylator metaphit (10 µM, 6/6). At 100 µM, metaphit (8/10) or the σR antagonist (+)-3-PPP (5/10) reversed AD block by 30 µM HAL but AD onset was delayed and its spread reduced. Thus, we cannot clearly demonstrate that AD block by HAL is mediated through a selective σR subtype.
We tested if HAL could also block oxygen glucose deprivation (OGD)-induced AD. 50 µM HAL blocked OGD-induced AD (7/16) or significantly delayed it but 100 µM HAL only delayed it (10/10). Therefore, ouabain- and OGD-induced AD are not equivalent models of simulated ischemia.
We tested if HAL could also block oxygen glucose deprivation (OGD)-induced AD. 50 µM HAL blocked OGD-induced AD (7/16) or significantly delayed it but 100 µM HAL only delayed it (10/10). Therefore, ouabain- and OGD-induced AD are not equivalent models of simulated ischemia.
Supported by Heart and Stroke Foundation and Glaxo Wellcome.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2002 Neuroscience Meeting Planner. Orlando, FL: Society for Neuroscience, 2002. Online.
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