Combined scopolamine and morphine treatment of traumatic brain injury in the rat.
Previous studies have indicated that either scopolamine (1.0 mg/kg) or morphine (10.0 mg/kg) administered to rats prior to or soon after moderate fluid percussion traumatic brain injury (TBI) reduces behavioral deficits associated with injury. In this study, a series of experiments examined the effects of a combination of these drugs, as well as each drug individually, on behavioral outcome, brain temperature, and systemic physiological responses to TBI. Experiment I: a single systemic bolus injection of scopolamine (n = 10), morphine (n = 11), scopolamine plus morphine (n = 11), or saline (n = 10) was administered to rats 15 min prior to TBI. Animals were assessed on beam-walking behavioral performance for 5 days after injury. Scopolamine alone or morphine alone significantly reduced (P < 0.05) deficits produced by injury. Treatment with a combination of scopolamine and morphine provided greater protection on beam-walking behavioral measures than either drug alone. Experiment II: morphine raised brain temperature in uninjured rats (n = 5) to a mean of 39.3 degrees C +/- 0.3 by 60 min post-injection. Neither scopolamine (n = 5) nor scopolamine plus morphine (n = 5) altered brain temperature. Experiment III: scopolamine (n = 7) significantly raised heart rate for 5 min after injury. Saline (n = 8), morphine (n = 9) and scopolamine plus morphine (n = 7) significantly lowered heart rate after injury. All four groups had similar hypertensive responses to TBI which peaked at 10 s after injury. The results confirm that pharmacological blockade of muscarinic receptors or stimulation of mu opioid receptors reduces functional deficits associated with TBI.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
B G
BG
Lyeth
S
S
Liu
R J
RJ
Hamm
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000008:administration & dosage*
D009020:Morphine; D012601:Scopolamine