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Stimulation of the Parapyramidal Region of the Neonatal Rat Brain Stem Produces Locomotor-Like Activity Involving Spinal 5-HT₇ and 5-HT_2A Receptors

Department of Physiology, Spinal Cord Research Centre, University of Manitoba Winnipeg, Manitoba, Canada

Submitted 7 February 2005; accepted in final form 3 May 2005

Locomotion can be induced in rodents by direct application 5-hydroxytryptamine (5-HT) onto the spinal cord. Previous studies suggest important roles for 5-HT₇ and 5-HT_2A receptors in the locomotor effects of 5-HT. Here we show for the first time that activation of a discrete population of 5-HT neurons in the rodent brain stem produces locomotion and that the evoked locomotion requires 5-HT₇ and 5-HT_2A receptors. Cells localized in the parapyramidal region (PPR) of the mid-medulla produced locomotor-like activity as a result of either electrical or chemical stimulation, and PPR-evoked locomotor-like activity was blocked by antagonists to 5-HT_2A and 5-HT₇ receptors located on separate populations of neurons concentrated in different rostro-caudal regions. 5-HT₇ receptor antagonists blocked locomotor-like activity when applied above the L₃ segment; 5-HT_2A receptor antagonists blocked locomotor-like activity only when applied below the L₂ segment. 5-HT₇ receptor antagonists decreased step cycle duration, consistent with an action on neurons involved in the rhythm-generating function of the central pattern generator (CPG) for locomotion. 5-HT_2A antagonists reduced the amplitude of ventral root activity with only small effects on step cycle duration, suggesting an action directly on cells involved in the output stage of the pattern generator for locomotion, including motoneurons and premotor cells. Experiments with selective antagonists show that dopaminergic (D₁, D₂) and noradrenergic (₁, ₂) receptors are not critical for PPR-evoked locomotor-like activity.

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