Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury

R. L. Hayes, L. W. Jenkins, Bruce G Lyeth, R. L. Balster, S. E. Robinson, G. L. Clifton, J. F. Stubbins, H. F. Young

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-D-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experimental traumatic brain injury (TBI). For the behavioral experiments, rats were administered either saline or PCP (1.0, 2.0, or 4.0 mg/kg, intrapentoneally [IP] 15 min before TBI. Rats were ventilated as necessary following injury. The duration of acute suppression of several reflexes (pinna, corneal, righting, and flexion) and responses (escape, head support, and spontaneous locomotion) was recorded for up to 70 min after trauma. Longer-term behavioral assessments (beam walking, beam balance, inclined plane, ambulatory activity, and body weight) were made for up to 10 days after trauma. PCP did not significantly alter the duration of acute behavioral suppression. At a dosage of 1.0 mg/kg, PCP significantly attenuated all long-term deficits except beam walking. Maximal protection against beam walking deficits was provided by the 4.0 mg/kg dosage of PCP. Sixty-three percent of saline-treated animals died within 10 days after injury. For rats pretreated with 1.0, 2.0, and 4.0 mg/kg of PCP, 40%, 23%, and 33% died, respectively. In physiologic experiments, pretreatment with 4.0 mg/kg of PCP (IP) 15 min before injury did not significantly affect systemic cardiovascular responses, plasma glucose levels, or blood gas levels observed within 30 min after injury. While the possibility of effects mediated by other neurotransmitter systems cannot be excluded, these data suggest that NMDA agonist-receptor interactions contribute to the pathophysiology of brain injury. In addition, neural mechanisms that mediate transient unconsciousness following moderate levels of head injury may differ from mechanisms that mediate more persistent neurologic deficits.

Original languageEnglish (US)
Pages (from-to)259-274
Number of pages16
JournalJournal of Neurotrauma
Volume5
Issue number4
StatePublished - 1988
Externally publishedYes

Fingerprint

Phencyclidine
N-Methylaspartate
Wounds and Injuries
Walking
Righting Reflex
Blinking
Unconsciousness
Locomotion
Neurologic Manifestations
N-Methyl-D-Aspartate Receptors
Craniocerebral Trauma
Brain Injuries
Neurotransmitter Agents
Traumatic Brain Injury
Gases
Head
Body Weight
Glucose

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. / Hayes, R. L.; Jenkins, L. W.; Lyeth, Bruce G; Balster, R. L.; Robinson, S. E.; Clifton, G. L.; Stubbins, J. F.; Young, H. F.

In: Journal of Neurotrauma, Vol. 5, No. 4, 1988, p. 259-274.

Research output: Contribution to journalArticle

Hayes, RL, Jenkins, LW, Lyeth, BG, Balster, RL, Robinson, SE, Clifton, GL, Stubbins, JF & Young, HF 1988, 'Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury', Journal of Neurotrauma, vol. 5, no. 4, pp. 259-274.
Hayes, R. L. ; Jenkins, L. W. ; Lyeth, Bruce G ; Balster, R. L. ; Robinson, S. E. ; Clifton, G. L. ; Stubbins, J. F. ; Young, H. F. / Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. In: Journal of Neurotrauma. 1988 ; Vol. 5, No. 4. pp. 259-274.
@article{d005e2ce350048cba5811b93933757fe,
title = "Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury",
abstract = "This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-D-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experimental traumatic brain injury (TBI). For the behavioral experiments, rats were administered either saline or PCP (1.0, 2.0, or 4.0 mg/kg, intrapentoneally [IP] 15 min before TBI. Rats were ventilated as necessary following injury. The duration of acute suppression of several reflexes (pinna, corneal, righting, and flexion) and responses (escape, head support, and spontaneous locomotion) was recorded for up to 70 min after trauma. Longer-term behavioral assessments (beam walking, beam balance, inclined plane, ambulatory activity, and body weight) were made for up to 10 days after trauma. PCP did not significantly alter the duration of acute behavioral suppression. At a dosage of 1.0 mg/kg, PCP significantly attenuated all long-term deficits except beam walking. Maximal protection against beam walking deficits was provided by the 4.0 mg/kg dosage of PCP. Sixty-three percent of saline-treated animals died within 10 days after injury. For rats pretreated with 1.0, 2.0, and 4.0 mg/kg of PCP, 40{\%}, 23{\%}, and 33{\%} died, respectively. In physiologic experiments, pretreatment with 4.0 mg/kg of PCP (IP) 15 min before injury did not significantly affect systemic cardiovascular responses, plasma glucose levels, or blood gas levels observed within 30 min after injury. While the possibility of effects mediated by other neurotransmitter systems cannot be excluded, these data suggest that NMDA agonist-receptor interactions contribute to the pathophysiology of brain injury. In addition, neural mechanisms that mediate transient unconsciousness following moderate levels of head injury may differ from mechanisms that mediate more persistent neurologic deficits.",
author = "Hayes, {R. L.} and Jenkins, {L. W.} and Lyeth, {Bruce G} and Balster, {R. L.} and Robinson, {S. E.} and Clifton, {G. L.} and Stubbins, {J. F.} and Young, {H. F.}",
year = "1988",
language = "English (US)",
volume = "5",
pages = "259--274",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "4",

}

TY - JOUR

T1 - Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury

AU - Hayes, R. L.

AU - Jenkins, L. W.

AU - Lyeth, Bruce G

AU - Balster, R. L.

AU - Robinson, S. E.

AU - Clifton, G. L.

AU - Stubbins, J. F.

AU - Young, H. F.

PY - 1988

Y1 - 1988

N2 - This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-D-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experimental traumatic brain injury (TBI). For the behavioral experiments, rats were administered either saline or PCP (1.0, 2.0, or 4.0 mg/kg, intrapentoneally [IP] 15 min before TBI. Rats were ventilated as necessary following injury. The duration of acute suppression of several reflexes (pinna, corneal, righting, and flexion) and responses (escape, head support, and spontaneous locomotion) was recorded for up to 70 min after trauma. Longer-term behavioral assessments (beam walking, beam balance, inclined plane, ambulatory activity, and body weight) were made for up to 10 days after trauma. PCP did not significantly alter the duration of acute behavioral suppression. At a dosage of 1.0 mg/kg, PCP significantly attenuated all long-term deficits except beam walking. Maximal protection against beam walking deficits was provided by the 4.0 mg/kg dosage of PCP. Sixty-three percent of saline-treated animals died within 10 days after injury. For rats pretreated with 1.0, 2.0, and 4.0 mg/kg of PCP, 40%, 23%, and 33% died, respectively. In physiologic experiments, pretreatment with 4.0 mg/kg of PCP (IP) 15 min before injury did not significantly affect systemic cardiovascular responses, plasma glucose levels, or blood gas levels observed within 30 min after injury. While the possibility of effects mediated by other neurotransmitter systems cannot be excluded, these data suggest that NMDA agonist-receptor interactions contribute to the pathophysiology of brain injury. In addition, neural mechanisms that mediate transient unconsciousness following moderate levels of head injury may differ from mechanisms that mediate more persistent neurologic deficits.

AB - This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-D-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experimental traumatic brain injury (TBI). For the behavioral experiments, rats were administered either saline or PCP (1.0, 2.0, or 4.0 mg/kg, intrapentoneally [IP] 15 min before TBI. Rats were ventilated as necessary following injury. The duration of acute suppression of several reflexes (pinna, corneal, righting, and flexion) and responses (escape, head support, and spontaneous locomotion) was recorded for up to 70 min after trauma. Longer-term behavioral assessments (beam walking, beam balance, inclined plane, ambulatory activity, and body weight) were made for up to 10 days after trauma. PCP did not significantly alter the duration of acute behavioral suppression. At a dosage of 1.0 mg/kg, PCP significantly attenuated all long-term deficits except beam walking. Maximal protection against beam walking deficits was provided by the 4.0 mg/kg dosage of PCP. Sixty-three percent of saline-treated animals died within 10 days after injury. For rats pretreated with 1.0, 2.0, and 4.0 mg/kg of PCP, 40%, 23%, and 33% died, respectively. In physiologic experiments, pretreatment with 4.0 mg/kg of PCP (IP) 15 min before injury did not significantly affect systemic cardiovascular responses, plasma glucose levels, or blood gas levels observed within 30 min after injury. While the possibility of effects mediated by other neurotransmitter systems cannot be excluded, these data suggest that NMDA agonist-receptor interactions contribute to the pathophysiology of brain injury. In addition, neural mechanisms that mediate transient unconsciousness following moderate levels of head injury may differ from mechanisms that mediate more persistent neurologic deficits.

UR - http://www.scopus.com/inward/record.url?scp=0024146867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024146867&partnerID=8YFLogxK

M3 - Article

VL - 5

SP - 259

EP - 274

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 4

ER -