Combined scopolamine and morphine treatment of traumatic brain injury in the rat

Bruce G Lyeth, Shanliang Liu, Robert J. Hamm

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


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 on uninjured rats (n = 5) to a mean of 39.3°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 μ opioid receptors reduces functional deficits associated with TBI. The greater protection observed with the combined drug treatment indicates that a cocktail of pharmacological treatments has the potential for providing greater benefit than single drug strategies.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalBrain Research
Issue number1
StatePublished - Jul 16 1993
Externally publishedYes


  • Fluid percussion
  • Morphine
  • Opioid
  • Scopolamine
  • Traumatic brain injury

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology
  • Clinical Neurology
  • Neuroscience(all)


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