Synergistic activation of the central pattern generator for locomotion by l-beta-3,4-dihydroxyphenylalanine and quipazine in adult paraplegic mice.
L-beta-3,4-Dihydroxyphenylalanine (L-DOPA) and quipazine, respectively dopamine/noradrenaline precursor and serotonergic (5-HT(2)) receptor agonist, were injected intraperitoneally in low-thoracic spinal mice at 7 days post-spinalization. In mice pre-treated with decarboxylase and monoamine oxydase inhibitors, L-DOPA (30-100 mg/kg) was found not to induce air-stepping. On the other hand, L-DOPA (40 mg/kg) consistently triggered locomotor-like movements if combined with low doses of quipazine (0.4-0.7 mg/kg) or if mice were placed on a motor-driven treadmill running at low speed. However, twitches, spasms, and other non-locomotor movements were also induced, especially on the treadmill. These results suggest that (1) spinal catecholaminergic and serotonergic receptors interact synergistically to generate locomotor-like movements in chronic spinal mice, and that (2) hindlimb afferent inputs associated with the treadmill conditions contribute to the genesis of locomotor-like and non-locomotor movements induced by these drugs.
Guertin
Pierre A
PA
Department of Anatomy and Physiology, Laval University, Neuroscience Research Center of Laval University Medical Center, Quebec City, Quebec, G1V4G2, Canada. pierre.guertin@crchul.ulaval.ca
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D010264:Paraplegia / Q000188:drug therapy* / Q000503:physiopathology; D011814:Quipazine / Q000494:pharmacology* / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000503:physiopathology
D007980:Levodopa; D011814:Quipazine