Modulation of Locomotor Activity by Multiple 5-HT and Dopaminergic Receptor Subtypes in the Neonatal Mouse Spinal Cord

• Published in: Journal of neurophysiology 2004-09, Vol.92 (3), p.1566-1576
• Main Authors: Madriaga, M. A, McPhee, L. C, Chersa, T, Christie, K. J, Whelan, P. J
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Dopamine Agents - pharmacology; Dose-Response Relationship, Drug; In Vitro Techniques; Mice; Motor Activity - drug effects; Motor Activity - physiology; Receptors, Dopamine - classification; Receptors, Dopamine - physiology; Receptors, Serotonin - classification; Receptors, Serotonin - physiology; Serotonin Agents - pharmacology; Spinal Cord - drug effects; Spinal Cord - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01181.2003

Calgary Brain Institute, Departments of Physiology and Biophysics, Clinical Neurosciences, University of Calgary, Alberta T2N 4N1, Canada Submitted 8 December 2003; accepted in final form 10 May 2004 Recently, it has been shown that bath-applied 5-HT can elicit fictive locomotion from perinatal mouse preparations. Since 5-HT acts on multiple receptor subtypes, the focus of this study was to examine which receptor families contribute to the genesis and modulation of locomotor activity. Blockade of 5-HT 2 (ketanserin or N -desmethylclozapine) or 5-HT 7 receptors (SB-269970) could reversibly block or modulate the locomotor-like pattern. A 5-HT 2 agonist ( -methyl-5-HT) was shown to be capable of activating the rhythm. Bath application of 5-HT 7 agonists (5-CT) generally led to a tonic increase in neurogram discharge, accompanied by bouts of rhythmic activity. Blockade of dopaminergic receptors {D 1 [ R -(+)-SCH-23390 or LE 300]/D 2 [(±)-sulpiride or L-741,626] } could reversibly disrupt the rhythm and most effectively did so when the D 1 and D 2 antagonists were added together. Conversely, 5-HT 2 and D 1 /D 2 agonists can interact to evoke locomotor activity. Overall, our data show that, in the neonatal mouse preparation, 5-HT evoked locomotion is partly dependent on activation of 5-HT 2 , 5-HT 7 , and dopaminergic receptor subtypes. Address for reprint requests and other correspondence: P. J. Whelan, Calgary Brain Institute, Dept. of Physiology and Biophysics and Clinical Neurosciences, 3330 Hospital Dr. NW, Calgary AB T2N 4N1, Canada (E-mail: whelan{at}ucalgary.ca ).