Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats
The novel antiepileptic drug gabapentin was designed as a structural analog of γ-aminobutyric acid (GABA). However, its mechanism of action remains unclear. In the present study, we investigated the effect of gabapentin on spinal reflexes in anesthetized rats. The mono- and polysynaptic reflex poten...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2004-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319325186 |
| _version_ | 1828385851361460224 |
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| author | Shinobu Shimizu Motoko Honda Mitsuo Tanabe Jun-Ichiro Oka Hideki Ono |
| author_facet | Shinobu Shimizu Motoko Honda Mitsuo Tanabe Jun-Ichiro Oka Hideki Ono |
| author_sort | Shinobu Shimizu |
| collection | DOAJ |
| description | The novel antiepileptic drug gabapentin was designed as a structural analog of γ-aminobutyric acid (GABA). However, its mechanism of action remains unclear. In the present study, we investigated the effect of gabapentin on spinal reflexes in anesthetized rats. The mono- and polysynaptic reflex potentials were recorded from the ipsilateral L5 ventral root after stimulation of the L5 dorsal root. The dorsal root reflex potential, an index of presynaptic inhibition, was recorded from the ipsilateral L4 dorsal root. In non-spinalized (intact) and spinalized rats, intravenously administered gabapentin reduced the mono- and polysynaptic reflex potentials in a dose-dependent manner. These inhibitory effects of gabapentin were not suppressed by the GABAA antagonist picrotoxin. Moreover, gabapentin also decreased spinal reflexes in spinalized rats depleted of spinal GABA with semicarbazide, an inhibitor of the GABA-synthesizing enzyme. The dorsal root reflex potentials were not affected by gabapentin. These results suggest that endogenous GABA does not mediate the inhibitory effects of gabapentin on spinal reflexes. Keywords:: spinal reflex, gabapentin, endogenous GABA, dorsal root reflex, pregabalin |
| first_indexed | 2024-12-10T05:27:01Z |
| format | Article |
| id | doaj.art-dcc778a2973a4906b7f5881948ee4491 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T05:27:01Z |
| publishDate | 2004-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-dcc778a2973a4906b7f5881948ee44912022-12-22T02:00:39ZengElsevierJournal of Pharmacological Sciences1347-86132004-01-01942137143Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in RatsShinobu Shimizu0Motoko Honda1Mitsuo Tanabe2Jun-Ichiro Oka3Hideki Ono4Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanLaboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanLaboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, JapanLaboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanLaboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan; Corresponding author. FAX: +81-52-836-3676 E-mail: hiono@phar.nagoya-cu.ac.jpThe novel antiepileptic drug gabapentin was designed as a structural analog of γ-aminobutyric acid (GABA). However, its mechanism of action remains unclear. In the present study, we investigated the effect of gabapentin on spinal reflexes in anesthetized rats. The mono- and polysynaptic reflex potentials were recorded from the ipsilateral L5 ventral root after stimulation of the L5 dorsal root. The dorsal root reflex potential, an index of presynaptic inhibition, was recorded from the ipsilateral L4 dorsal root. In non-spinalized (intact) and spinalized rats, intravenously administered gabapentin reduced the mono- and polysynaptic reflex potentials in a dose-dependent manner. These inhibitory effects of gabapentin were not suppressed by the GABAA antagonist picrotoxin. Moreover, gabapentin also decreased spinal reflexes in spinalized rats depleted of spinal GABA with semicarbazide, an inhibitor of the GABA-synthesizing enzyme. The dorsal root reflex potentials were not affected by gabapentin. These results suggest that endogenous GABA does not mediate the inhibitory effects of gabapentin on spinal reflexes. Keywords:: spinal reflex, gabapentin, endogenous GABA, dorsal root reflex, pregabalinhttp://www.sciencedirect.com/science/article/pii/S1347861319325186 |
| spellingShingle | Shinobu Shimizu Motoko Honda Mitsuo Tanabe Jun-Ichiro Oka Hideki Ono Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats Journal of Pharmacological Sciences |
| title | Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats |
| title_full | Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats |
| title_fullStr | Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats |
| title_full_unstemmed | Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats |
| title_short | Endogenous GABA Does Not Mediate the Inhibitory Effects of Gabapentin on Spinal Reflexes in Rats |
| title_sort | endogenous gaba does not mediate the inhibitory effects of gabapentin on spinal reflexes in rats |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319325186 |
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