Neuroscience 2001 Abstract
| Presentation Number: | 297.13 |
|---|---|
| Abstract Title: | EVIDENCE OF 5-HT INDUCED LOCOMOTION BY 5-HT RECEPTOR INDEPENDENT MECHANISMS. |
| Authors: |
Aduonum, A. D.*1
; Dougherty, K. J.1
; Machacek, D. W.1
; Hochman, S.1
1Physiol, Emory Univ Sch Med, Atlanta, GA |
| Primary Theme and Topics |
Motor Systems - Spinal Cord |
| Secondary Theme and Topics | Motor Systems<br />- Locomotion |
| Session: |
297. Spinal cord: pattern generation I Poster |
| Presentation Time: | Monday, November 12, 2001 8:00 AM-9:00 AM |
| Location: | Exhibit Hall OO-9 |
| Keywords: | serotonin, spinal cord, NMDA, rat |
We previously implicated 5-HT7 receptors in 5-HT-induced locomotion (Cina & Hochman 1998 SFN). This observation was supported by other studies (Fyda & Jordan 1999 SFN; Fyda et al 2000 SFN). In those studies, Sprague Dawley rats were obtained from Charles River (Montreal). Another study connected 5-HT1 and 5-HT2 receptors to locomotion (Cazalets et al 1992 J Physiol). Since neurophysiological differences within and between rat strains have been noted (e.g. Xu et al 2001 Pain), we examined the pharmacology of 5-HT locomotion in Sprague Dawley and Wistar rats obtained from a different source (Charles River, NC).
Experiments were employed in the isolated rat spinal cord (days 0-3). Dual L2 & L5 ventral root recordings monitored motor output. While NMDA alone (2-5 μM) never induced locomotion, the addition of 5-HT (10 - 40 μM) produced a stable long-lasting locomotor rhythm in all preparations.
The following 5-HT receptor antagonists alone or in combination were incapable of blocking locomotion (≦1 μM): (i) Sprague Dawley; Ro-046790 (5-HT6), RS-39604 (5-HT4), methiothepin (5-HT1,2,5,6,7), clozapine (5-HT2A/C,3,6,7) & normethyl-clozapine (5-HT2C). (ii) Wistar: NAN-190 (5-HT1A), ritanserin (5-HT2,6,7), methiothepin (5-HT1,2,5,6,7), RS-39604 (5-HT4) & pindolol (5-HT1A,1B).
Thus, in these rats, 5-HT appears to contribute to locomotion independent of activation of known 5-HT receptors. 5-HT binds to D1 receptors and addition of dopamine prevented stable locomotion. However, the D1 receptor antagonist SCH23390 did not block ongoing 5-HT evoked locomotion. We are exploring the possibility of modulatory actions of 5-HT on other unidentified binding sites.
Experiments were employed in the isolated rat spinal cord (days 0-3). Dual L2 & L5 ventral root recordings monitored motor output. While NMDA alone (2-5 μM) never induced locomotion, the addition of 5-HT (10 - 40 μM) produced a stable long-lasting locomotor rhythm in all preparations.
The following 5-HT receptor antagonists alone or in combination were incapable of blocking locomotion (≦1 μM): (i) Sprague Dawley; Ro-046790 (5-HT6), RS-39604 (5-HT4), methiothepin (5-HT1,2,5,6,7), clozapine (5-HT2A/C,3,6,7) & normethyl-clozapine (5-HT2C). (ii) Wistar: NAN-190 (5-HT1A), ritanserin (5-HT2,6,7), methiothepin (5-HT1,2,5,6,7), RS-39604 (5-HT4) & pindolol (5-HT1A,1B).
Thus, in these rats, 5-HT appears to contribute to locomotion independent of activation of known 5-HT receptors. 5-HT binds to D1 receptors and addition of dopamine prevented stable locomotion. However, the D1 receptor antagonist SCH23390 did not block ongoing 5-HT evoked locomotion. We are exploring the possibility of modulatory actions of 5-HT on other unidentified binding sites.
Supported by NINDS #NS40440-01. ADA by PREP at Emory
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2001 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2001. Online.
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