PT - JOURNAL ARTICLE AU - Nicolas P. Lapointe AU - Roth-Visal Ung AU - Pascal Rouleau AU - Pierre A. Guertin TI - Effects of Spinal α<sub>2</sub>-Adrenoceptor and I<sub>1</sub>-Imidazoline Receptor Activation on Hindlimb Movement Induction in Spinal Cord-Injured Mice AID - 10.1124/jpet.107.134874 DP - 2008 Jun 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 994--1006 VI - 325 IP - 3 4099 - http://jpet.aspetjournals.org/content/325/3/994.short 4100 - http://jpet.aspetjournals.org/content/325/3/994.full SO - J Pharmacol Exp Ther2008 Jun 01; 325 AB - 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. The American Society for Pharmacology and Experimental Therapeutics