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

Abstract

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-HT2 (ketanserin or N-desmethylclozapine) or 5-HT7 receptors (SB-269970) could reversibly block or modulate the locomotor-like pattern. A 5-HT2 agonist (α-methyl-5-HT) was shown to be capable of activating the rhythm. Bath application of 5-HT7 agonists (5-CT) generally led to a tonic increase in neurogram discharge, accompanied by bouts of rhythmic activity. Blockade of dopaminergic receptors {D1 [ R-(+)-SCH-23390 or LE 300]/D2 [(±)-sulpiride or L-741,626] } could reversibly disrupt the rhythm and most effectively did so when the D1 and D2 antagonists were added together. Conversely, 5-HT2 and D1/D2 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-HT2, 5-HT7, and dopaminergic receptor subtypes.