Dose dependence of the 5-HT agonist quipazine in facilitating spinal stepping in the rat with epidural stimulation

• Published in: Neuroscience letters Vol. 438; no. 3; pp. 281 - 285
• Main Authors: Ichiyama, Ronaldo M., Gerasimenko, Yury, Jindrich, Devin L., Zhong, Hui, Roy, Roland R., Edgerton, V. Reggie
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 27.06.2008
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - radiation effects; Disease Models, Animal; Dose-Response Relationship, Drug; Electric Stimulation Therapy; Epidural electrical stimulation; Epidural Space; Female; Locomotion; Locomotion - drug effects; Locomotion - physiology; Locomotion - radiation effects; Lower Extremity - physiopathology; Lower Extremity - radiation effects; Lumbosacral Region; Psychomotor Performance - drug effects; Psychomotor Performance - radiation effects; Quipazine - administration & dosage; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin Receptor Agonists - administration & dosage; Spinal cord; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Rats; Locomotion; Epidural electrical stimulation; Spinal cord; Serotonin
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2008.04.080

Epidural electrical stimulation (ES) at spinal cord segment L2 can produce coordinated step-like movements in completely spinalized adult rats [R.M. Ichiyama, Y.P. Gerasimenko, H. Zhong, R.R. Roy, V.R. Edgerton, Hindlimb stepping movements in complete spinal rats induced by epidural spinal cord stimulation, Neurosci. Lett. 383 (2005) 339–344]. Plantar placement of the paws, however, was rarely observed. Here, we sought to determine the dose dependence of a 5-HT agonist (quipazine) on stepping kinematics when administered in combination with ES. Six adult female Sprague–Dawley rats received a complete mid-thoracic spinal cord transection and were implanted with epidural electrodes at the L2 spinal cord level. Quipazine (i.p.) was tested at doses of 0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg. Rats were placed in a body weight support system, allowing them to walk bipedally on a moving treadmill belt (7 cm/s). 3D step kinematics analysis revealed that coordinated alternating bilateral stepping was induced by L2 stimulation (50 Hz) alone and by quipazine alone. Furthermore, the combination treatment produced significantly greater numbers of plantar steps and improved quality of stepping compared to either intervention alone. Both number and quality of stepping peaked at the intermediate dose of 0.3–0.4 mg/kg. The results indicate that quipazine and ES can have complementary effects on spinal circuits and that quipazine dosage is an important factor in differentially modulating these circuitries to improve the quality of the bipedal stepping on a treadmill belt.