5‐HT1A receptors are involved in short‐ and long‐term processes responsible for 5‐HT‐induced locomotor function recovery in chronic spinal rat

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Abstract
After thoracic spinal cord transection, a paraplegic syndrome occurs. Previous data showed that an acute administration of a 5‐HT2 agonist (quipazine) could promote motor function recovery in spinal rats. However, continuous subdural perfusion of quipazine via an osmotic pump over 1 month proved to be more effective. The present study was designed to investigate the possible involvement of 5‐HT1A receptors in such recovery. Motor performances and locomotor parameters were analysed in spinal animals receiving daily, for 1 month, a dose of the 5‐HT1A agonist 8‐OHDPAT. The results were compared to those obtained in spinal rats receiving either a placebo or quipazine in the same conditions. Using daily injections instead of continuous perfusion of either receptor agonist to spinal animals allowed characterization of short‐ and long‐term consequences of pharmacological stimulation of 5‐HT1A and 5‐HT2 receptors on motor function recovery. Our data demonstrate that daily injections of a 5‐HT1A agonist induce long‐term, cumulative, positive effects on motor function recovery, as assessed by the improvement in the walking parameters observed before the ‘day‐test’ injection. This might involve use‐dependent processes depending on a chronic and/or repetitive stimulation of the spinal network for locomotion in relation to 5‐HT receptor activation. A further improvement in the motor parameters, transiently observed following the injection, suggests a more direct action of 5‐HT1A and 5‐HT2 receptor activation on spinal neurons involved in motor pattern generation.

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