Specific role of dopamine D1 receptors in spinal network activation and rhythmic movement induction in vertebrates

Dopamine (DA) is well-recognized for its determinant role in the modulation of various brain functions. DA was also found in in vitro isolated invertebrate preparations to activate per se the central pattern generator for locomotion. However, it is less clear whether such a role as an activator of central neural circuitries exists in vertebrate species. Here, we studied in vivo the effects induced by selective DA receptor agonists and antagonists on hindlimb movement generation in mice completely spinal cord-transected (Tx) at the low-thoracic level (Th9/10). Administration of D1/D5 receptor agonists (0.5-2.5 mg kg(-1), i.p.) was found to acutely elicit rhythmic locomotor-like movements (LMs) and non-locomotor movements (NLMs) in untrained and non-sensory stimulated animals. Comparable effects were found in mice lacking the D5 receptor (D5KO) whereas D1/D5 receptor antagonist-pretreated animals (wild-type or D5KO) failed to display D1/D5 agonist-induced LMs. In contrast, administration of broad spectrum or selective D2, D3 or D4 agonists consistently failed to elicit significant hindlimb movements. Overall, the results clearly show in mice the existence of a role for D1 receptors in spinal network activation and corresponding rhythmic movement generation.