Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats
Applying serotonergic (5-HT) agonists or grafting of fetal serotonergic cells into the spinal cord improves locomotion after spinal cord injury. Little is known about the role of 5-HT receptors in the control of voluntary locomotion, so we administered inverse agonists of 5-HT2 (Cyproheptadine; Cypr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Neural Circuits |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncir.2020.00014/full |
| _version_ | 1818108020085751808 |
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| author | Henryk Majczyński Anna M. Cabaj Larry M. Jordan Urszula Sławińska |
| author_facet | Henryk Majczyński Anna M. Cabaj Larry M. Jordan Urszula Sławińska |
| author_sort | Henryk Majczyński |
| collection | DOAJ |
| description | Applying serotonergic (5-HT) agonists or grafting of fetal serotonergic cells into the spinal cord improves locomotion after spinal cord injury. Little is known about the role of 5-HT receptors in the control of voluntary locomotion, so we administered inverse agonists of 5-HT2 (Cyproheptadine; Cypr), 5-HT2A neutral antagonist (Volinanserin; Volin), 5-HT2C neutral antagonist (SB 242084), and 5-HT2B/2C inverse agonist (SB 206553) receptors intrathecally in intact rats and monitored their effects on unrestrained locomotion. An intrathecal cannula was introduced at the low thoracic level and pushed caudally until the tip reached the L2/L3 or L5/L6 spinal segments. Locomotor performance was evaluated using EMG activity of hindlimb muscles during locomotion on a 2 m long runway. Motoneuron excitability was estimated using EMG recordings during dorsi- and plantar flexion at the ankle. Locomotion was dramatically impaired after the blockage of 5-HT2A receptors. The effect of Cypr was more pronounced than that of Volin since in the L5/L6 rats Cypr (but not Volin) induced significant alteration of the strength of interlimb coordination followed by total paralysis. These agents significantly decreased locomotor EMG amplitude and abolished or substantially decreased stretch reflexes. Blocking 5-HT2B/2C receptors had no effect either on locomotion or reflexes. We suggest that in intact rats serotonin controls timing and amplitude of muscle activity by acting on 5-HT2A receptors on both CPG interneurons and motoneurons, while 5-HT2B/2C receptors are not involved in control of the locomotor pattern in lumbar spinal cord. |
| first_indexed | 2024-12-11T02:08:43Z |
| format | Article |
| id | doaj.art-14b90a7acecf4d968b21a5b4aec1b11d |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-12-11T02:08:43Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-14b90a7acecf4d968b21a5b4aec1b11d2022-12-22T01:24:19ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102020-04-011410.3389/fncir.2020.00014514715Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact RatsHenryk Majczyński0Anna M. Cabaj1Larry M. Jordan2Urszula Sławińska3Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandDepartment of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, CanadaNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandApplying serotonergic (5-HT) agonists or grafting of fetal serotonergic cells into the spinal cord improves locomotion after spinal cord injury. Little is known about the role of 5-HT receptors in the control of voluntary locomotion, so we administered inverse agonists of 5-HT2 (Cyproheptadine; Cypr), 5-HT2A neutral antagonist (Volinanserin; Volin), 5-HT2C neutral antagonist (SB 242084), and 5-HT2B/2C inverse agonist (SB 206553) receptors intrathecally in intact rats and monitored their effects on unrestrained locomotion. An intrathecal cannula was introduced at the low thoracic level and pushed caudally until the tip reached the L2/L3 or L5/L6 spinal segments. Locomotor performance was evaluated using EMG activity of hindlimb muscles during locomotion on a 2 m long runway. Motoneuron excitability was estimated using EMG recordings during dorsi- and plantar flexion at the ankle. Locomotion was dramatically impaired after the blockage of 5-HT2A receptors. The effect of Cypr was more pronounced than that of Volin since in the L5/L6 rats Cypr (but not Volin) induced significant alteration of the strength of interlimb coordination followed by total paralysis. These agents significantly decreased locomotor EMG amplitude and abolished or substantially decreased stretch reflexes. Blocking 5-HT2B/2C receptors had no effect either on locomotion or reflexes. We suggest that in intact rats serotonin controls timing and amplitude of muscle activity by acting on 5-HT2A receptors on both CPG interneurons and motoneurons, while 5-HT2B/2C receptors are not involved in control of the locomotor pattern in lumbar spinal cord.https://www.frontiersin.org/article/10.3389/fncir.2020.00014/fullserotoninantagonistinverse agonistspinal cordintrathecal application |
| spellingShingle | Henryk Majczyński Anna M. Cabaj Larry M. Jordan Urszula Sławińska Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats Frontiers in Neural Circuits serotonin antagonist inverse agonist spinal cord intrathecal application |
| title | Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats |
| title_full | Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats |
| title_fullStr | Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats |
| title_full_unstemmed | Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats |
| title_short | Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats |
| title_sort | contribution of 5 ht2 receptors to the control of the spinal locomotor system in intact rats |
| topic | serotonin antagonist inverse agonist spinal cord intrathecal application |
| url | https://www.frontiersin.org/article/10.3389/fncir.2020.00014/full |
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