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)
Lyeth
B G
BG
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Liu
S
S
Hamm
R J
RJ
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