Alpha(2)-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride. Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury. The aim of this study was to analyze the role of α(2)-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage. The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours, 3 days, and 20 days after ferrous chloride-induced cortical injury: saline, clonidine, efaroxan (a selective antagonist of α(2)-adrenergic receptors) and clonidine + efaroxan. The sensorimotor score, the immunohistochemical staining for α(2A)-adrenergic receptors, and norepinephrine levels were evaluated. Eight hours post-injury, the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased, and these effects were maintained 3 days post-injury. However, 20 days later, clonidine administration diminished norepinephrine levels in the pons compared with the sham group. This effect was accompanied by sensorimotor deficits. These effects were blocked by efaroxan. In conclusion, an increase in α(2)-adrenergic receptor levels was observed after injury. Clonidine restores motor deficits in rats recovering from cortical injury, an effect that was prevented by efaroxan. The underlying mechanisms involve the stimulation of hypersensitive α(2)-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus. The results of this study suggest that α(2) receptor agonists might restore deficits or impede rehabilitation in patients with brain injury, and therefore pharmacological therapies need to be prescribed cautiously to these patients.