Effects of scopolamine treatment on long-term behavioral deficits following concussive brain injury to the rat.

Scopolamine (0.1, 1.0, or 10.0 mg/kg) or saline was systemically (i.p.) administered to rats 15 min prior to concussive fluid percussion brain injury. Animals pretreated with the 1.0 mg/kg dose exhibited significantly (P less than 0.05) less motor deficits and less body weight loss and recovered to baseline performance sooner than saline-treated rats. Mortality and associated convulsions were significantly lower in rats pretreated with the 1.0 mg/kg dose of scopolamine. A 1.0 mg/kg dose of scopolamine administered (i.p.) 30 s after injury also significantly reduced behavioral deficits. No differences were observed between saline- and scopolamine-treated animals in either the incidence or duration of transient apnea following injury. A 1.0 mg/kg dose of scopolamine administered (i.p.) 15 min prior to epidural clip compression of the spinal cord had no effect on the severity of motor function deficits assessed by an inclined plane test. The data from these experiments suggest muscarinic cholinergic involvement in at least some of the long-term behavioral deficits following mild and moderate levels of brain injury. These results suggest that muscarinic cholinergic antagonists may prove beneficial in the treatment of human head injury.