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

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-HT₂ (ketanserin or N-desmethylclozapine) or 5-HT₇ receptors (SB-269970) could reversibly block or modulate the locomotor-like pattern. A 5-HT₂ agonist (-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.

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