Growing evidence from in vitro studies suggests that spinal serotonin (5-HT) receptor subtypes 5-HTR(1A) and 5-HTR(7) are associated with an induction of central pattern generator activity. However, the possibility of a specific role for these receptor subtypes in locomotor rhythmogenesis in vivo remains unclear. Here, we studied the effects of a single dose (1 mg/kg, i.p.) of 8-hydroxy-2-(di-N-propylamino)-tetralin (8-OH-DPAT), a potent and selective 5-HTR(1A/7) agonist, in mice spinal cord transected at the low-thoracic level (Th9/10). The results show that 8-OH-DPAT acutely induced, within 15 min, hindlimb movements that share some characteristics with normal locomotion. Paraplegic mice pretreated with the selective 5-HTR(1A) antagonists, WAY100,135 or WAY100,635, displayed significantly less 8-OH-DPAT-induced movement. A similar reduction of 8-OH-DPAT-induced movements was found in animals pretreated with SB269970, a selective 5-HTR(7) antagonist. Moreover, a near complete blockade of 8-OH-DPAT-induced movement was obtained in wild-type mice pretreated with 5-HTR(1A) and 5-HTR(7) antagonists, and in 5-HTR(7)-/- mice pretreated with 5-HTR(1A) antagonists. Overall, these results clearly demonstrate that 8-OH-DPAT potently induces locomotor-like movement in the previously paralysed hindlimbs of low-thoracic-transected mice. The results, with selective antagonists and knockout animals, provide compelling evidence of a specific contribution of both receptor subtypes to spinal locomotor rhythmogenesis in vivo.

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A role of serotonin receptors (5-HTRs) in spinal rhythmogenesis has been proposed several years ago based mainly upon data showing that bath-applied 5-HT could elicit locomotor-like rhythms in in vitro isolated spinal cord preparations. Such a role was partially confirmed in vivo after revealing that systemically administered 5-HTR(2) agonists, such as quipazine, could induce some locomotor-like movements (LM) in completely spinal cord-transected (Tx) rodents. However, given the limited binding selectivity of currently available 5-HTR(2) agonists, it has remained difficult to determine clearly if one receptor subtype is specifically associated with LM induction. In situ hybridization, data using tissues from L1-L2 spinal cord segments, where critical locomotor network elements have been identified in mice, revealed greater 5-HTR(2A) mRNA levels in low-thoracic Tx than non-Tx animals. This expression level remained elevated for several days, specifically in the lateral intermediate zone, where peak values were detected at 1 week post-Tx and returned to normal at 3 weeks post-Tx. Behavioral and kinematic analyses revealed quipazine-induced LM in 1-week Tx mice either non-pretreated or pretreated with selective 5-HTR(2B) and/or 5-HTR(2C) antagonists. In contrast, LM completely failed to be induced by quipazine in animals pretreated with selective 5-HTR(2A) antagonists. Altogether, these results provide strong evidence suggesting that 5-HTR(2A) are specifically associated with spinal locomotor network activation and LM generation induced by quipazine in Tx animals. These findings may contribute to design drug treatments aimed at promoting locomotor function recovery in chronic spinal cord-injured patients.

Patients with spinal cord injury (SCI) typically experience body weight loss, motor function deficits, and a general decline of physical fitness. Animal models with these characteristics can serve to study the detailed adaptive changes following SCI. In the present study, we report the use of an adult paraplegic mouse model to study SCI-induced changes. We characterized the early effects of complete thoracic spinal cord transection on (1) whole body weight, (2) forelimb and hindlimb weight and volume, and (3) contractile properties of hindlimb extensor muscle. Drastic changes were found at 7 days post-spinal cord transection. These included a 24% loss in whole body weight accompanied by a large decrease of weight and volume in the forelimbs and the hindlimbs. We also observed in the soleus muscle, a 32% decrease in mass and maximal tetanic tension (Po) as well as a 21% and 48% increase in time-to-peak tension (TPT) and half-relaxation time (1/2 RT) respectively. After 28 days, all of the changes remained, except for 1/2 RT and TPT which nearly returned to control levels. Altogether, the results reveal that large changes in body weight, limb size and musculoskeletal properties occur within only one week after complete spinal cord transection. The use of paraplegic mouse models may provide new therapeutic approaches to restore motor and locomotor functions after SCI.

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Résumé Les substances psychotropes comme la cocaïne peuvent agir à titre de stimulant sur le système nerveux central et altérer la réponse et les comportements sexuels. Plusieurs études ont suggéré un lien entre les effets de la cocaïne et la sexualité, mais les résultats restent contradictoires entre ses effets positifs et négatifs. Dans cette étude exploratoire, l’impact des substances psychotropes, dont la cocaïne, sur la sexualité a été exploré auprès de 33 participants fréquentant un centre de réadaptation en toxicomanie. Des corrélations ont été effectuées entre divers aspects de leur consommation, incluant la durée, le mode d’administration, la quantité et la fréquence de leur utilisation et divers aspects de leur sexualité, notamment les fantasmes, la satisfaction sexuelle, les comportements sexuels atypiques et la criminalité. Les résultats montrent des corrélations significatives entre les variables de consommation et celles liées à la satisfaction sexuelle, les comportements atypiques et la criminalité. Plus précisément, les résultats suggèrent qu’une augmentation de la durée de consommation ou des quantités absorbées est associée à une diminution de la satisfaction sexuelle, et qu’une augmentation de la durée de consommation ou du mode d’administration à taux d’absorption élevé est associée à un accroissement des comportements sexuels atypiques et des comportements de criminalité. Ces résultats sont interprétés en fonction d’un modèle explicatif qui tente d’intégrer les résultats de l’étude avec ceux parfois contradictoires de la documentation scientifique.

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