Abstract
A partial recovery of locomotor functions has been shown in spinal cord-transected (Tx) cats after regular treadmill training and repeated administration of clonidine, an α2-adrenoreceptor agonist. However, clonidine has generally failed to show prolocomotor effects in other models (e.g., rat or mudpuppy in vitro-isolated spinal cord preparations). The reasons for this discrepancy remain unclear, but they may suggest condition- or species-specific effects induced by clonidine. This study is aimed at examining both the acute (at 6 or 41 days post-Tx) and chronic effects of repeated (once a week for one month) clonidine administration (0.25–5.0 mg/kg i.p.) on hindlimb movement generation in Tx mice (thoracic segment9/10). Locomotor-like (LM) and nonlocomotor movements (NLM) were assessed both in open-field and treadmill conditions. The results show that clonidine consistently failed, in both conditions, to induce LM and NLM at all time points even though control experiments revealed hindlimb movements steadily induced by 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a serotonin receptor agonist. In turn, clonidine acutely suppressed (I1-imidazoline receptor-mediated) the frequency of spontaneously occurring LM and NLM but apparently increased spinal excitability over time, because the frequency of spontaneous LM and NLM was significantly greater in clonidine-treated (before an injection) than vehicle-treated animals after repeated administration for a few weeks. The results clearly show that clonidine can not acutely induce hindlimb movements in untrained and otherwise nonstimulated (e.g., no tail or perineal pinching) Tx mice, although repeated administration may progressively facilitate the expression of spontaneous hindlimb movements.
Footnotes
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This study was supported by the Canadian Institutes of Health Research and the Fond de Recherche en Sante du Quebec (FRSQ). N.P.L. and R.-V.U. received studentships from the FRSQ.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.134874.
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ABBREVIATIONS: SCI, spinal cord injury; Tx, spinal cord-transection; CPG, central pattern generator; 8-OH-DPAT, 8-hydroxy-2-(di-N-propylamino)-tetralin; ACOS, Average Combined Score; NLM, nonlocomotor movement; LM, locomotor-like movement; AOB, Antri, Orsal, Barthe locomotor scale; 5-HT1A/7, serotonin-type 1A and 7 receptor.
- Received November 30, 2007.
- Accepted March 24, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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