Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms

NEUROPHARMACOLOGY

卷:101

Article

Acevedo, JeanMarie ; Santana-Almansa, Alexandra ; Matos-Vergara, Nikol ; Marrero-Cordero, Luis Rene ; Cabezas-Bou, Ernesto ; Diaz-Rios, Manuel

关键词: Caffeine;    Locomotion;    Spinal cord;    Adenosine;    Mouse;    Dopamine;   

DOI  :  10.1016/j.neuropharm.2015.10.020

来源: Elsevier

【 摘 要 】

Caffeine is a potent psychostimulant that can have significant and widely variable effects on the activity of multiple neuronal pathways. The most pronounced caffeine-induced behavioral effect seen in rodents is to increase locomotor activity which has been linked to a dose-dependent inhibition of A(1) and A(2A) receptors. The effects of caffeine at the level of the lumbar spinal central pattern generator (CPG) network for hindlimb locomotion are lacking. We assessed the effects of caffeine to the locomotor function of the spinal CPG network via extracellular ventral root recordings using the isolated neonatal mouse spinal cord preparation. Addition of caffeine and of an A1 receptor antagonist significantly decreased the cycle period accelerating the ongoing locomotor rhythm, while decreasing burst duration reversibly in most preparations suggesting the role of A1 receptors as the primary target of caffeine. Caffeine and an A1 receptor antagonist failed to stimulate ongoing locomotor activity in the absence of dopamine or in the presence of a D-1 receptor antagonist supporting A(1)/D-1 receptor-dependent mechanism of action. The use of caffeine or an A(1) receptor blocker failed to stimulate an ongoing locomotor rhythm in the presence of a blocker of the cAMP-dependent protein kinase (PICA) supporting the need of this intracellular pathway for the modulatory effects of caffeine to occur. These results support a stimulant effect of caffeine on the lumbar spinal network controlling hindlimb locomotion through the inhibition of A1 receptors and subsequent activation of D1 receptors via a PICA-dependent intracellular mechanism. (C) 2015 Elsevier Ltd. All rights reserved.

【 授权许可】

Free