The effect of M1 muscarinic blockade on behavior and physiological responses following traumatic brain injury in the rat.
Dicyclomine (1 mg/kg or 10 mg/kg), scopolamine (1 mg/kg), or saline was administered intraperitoneally to rats 15 min prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. All 3 antimuscarinic treatments reduced the duration of transient behavioral suppression as assessed by these measures. It appears that blockade of the M1 muscarinic receptor can attenuate transient behavioral suppression associated with concussive brain injury. Thus, stimulation of M1 muscarinic receptors may mediate components of reversible traumatic unconsciousness following cerebral concussion. No differences were observed between saline and antimuscarinic treatments in the incidence or duration of apnea following injury. Scopolamine pretreatment significantly elevated heart rate prior to injury, but had no significant effect on the responses of heart rate and blood pressure to experimental concussion. Both doses of dicyclomine significantly reduced resting heart rate, but unlike scopolamine, significantly enhanced the cardiovascular response to fluid percussion injury. Antimuscarinic treatment significantly reduced body weight loss and certain motor deficits, including beam balance and beam walk performance, following concussive head injury. Scopolamine and both doses of dicyclomine appeared to be equally effective in reducing long-term deficits. Data from these experiments indicate that at least some of the long-term behavioral deficits following moderate levels of brain injury may involve the binding of acetylcholine to M1 muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Robinson
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SE
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Foxx
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SD
Posner
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Martin
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Davis
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Guo
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Enters
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D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000503:physiopathology; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004025:Dicyclomine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009069:Movement Disorders / Q000209:etiology* / Q000378:metabolism; D018727:Muscarinic Antagonists; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology* / Q000627:therapeutic use
D003509:Cyclohexanecarboxylic Acids; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D004025:Dicyclomine; D012601:Scopolamine