RESUMEN
In chronic spinal rats, long-term stimulation of 5-HT receptors with quipazine or 8-OHDPAT by means of daily injection, promotes robust locomotor recovery. The question of a possible potentiation between treatments when applied together was addressed. Daily injections of both 8-OHDPAT and quipazine, were performed for a month in spinal animals. Animals were placed on a treadmill and the bipedal hindlimb locomotion was tested. Motor performances (behavioural test) and locomotor parameters (EMG and kinematic) were analysed weekly during the treatment. Furthermore, the locomotor performances were evaluated during two supplemental months following the end of the treatment. Our results suggest that association of both agonists induced long-lasting positive effects on locomotor function. Motor performances were significantly better after combined injection of both drugs than when the agonists were used separately. But, the most significant and new result is that the locomotor scores did not decrease during the weeks that followed the end of the treatment. These results suggests a long-lasting and 5-HT-dependent reorganisation of spinal networks.
Asunto(s)
8-Hidroxi-2-(di-n-propilamino)tetralin/administración & dosificación , Actividad Motora/efectos de los fármacos , Quipazina/administración & dosificación , Recuperación de la Función/efectos de los fármacos , Agonistas de Receptores de Serotonina/administración & dosificación , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Conducta Animal/efectos de los fármacos , Enfermedad Crónica , Vías de Administración de Medicamentos , Esquema de Medicación , Quimioterapia Combinada , Electromiografía/métodos , Femenino , Locomoción/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/fisiopatología , Factores de TiempoRESUMEN
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.
Asunto(s)
Locomoción/efectos de los fármacos , Receptor de Serotonina 5-HT1A/fisiología , Recuperación de la Función/efectos de los fármacos , Serotonina/farmacología , Traumatismos de la Médula Espinal/fisiopatología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Conducta Animal , Fenómenos Biomecánicos , Electromiografía/métodos , Femenino , Miembro Posterior/fisiopatología , Locomoción/fisiología , Actividad Motora/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Quipazina/farmacología , Ratas , Agonistas de Receptores de Serotonina/farmacología , Traumatismos de la Médula Espinal/tratamiento farmacológico , Factores de Tiempo , Grabación de Cinta de VideoAsunto(s)
Locomoción/fisiología , Actividad Motora/fisiología , Neuronas/trasplante , Traumatismos de la Médula Espinal/terapia , Animales , Fármacos Neuroprotectores/uso terapéutico , Ratas , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/rehabilitación , Trasplante de Células MadreRESUMEN
A complete transection of the spinal cord at a low thoracic level induces a paraplegic syndrome that is accompanied by a loss of spinal cord serotonin content. Former experimental data suggest that the central pattern generator for locomotion, located in the lumbar segments of the spinal cord, might be able to generate rhythmic motor outputs (similar to automatic walking under certain circumstances) involving exteroceptive stimulations and activation of serotonergic receptors. In the present study, we investigated the effects of a chronic treatment using a serotonergic agonist, delivered continuously to the sublesionned spinal cord, and its effect on motor function recovery. The data obtained from behavioural, kinematic and electromyographic measurements suggest that the chronic stimulation of 5-HT2 type receptors allows motor function recovery. Behavioural measurements show a clear improvement in motor performances when compared to spinal animals (confirmed by kinematic observations): alternating steps and foot placement is recovered in these animals. However, electromyographic data demonstrate that the pattern of activation of the muscles is only restored partially.