Lubeluzole and conditioned learning after cerebral ischemia

Rashmi N. Mueller, Donald J. Deyo, David R. Brantley, John F. Disterhoft, Mark Zornow

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Lubeluzole [S-4-(2-benzothiazolylmethylamino)-α -((3,4-difluorophenoxy)methyl)-1-piperidineethanol] reduces the severity of cerebral injury in animal models of brain ischemia. Its beneficial effects may include decreased concentration of extracellular glutamate, blockade of sodium and calcium channels, and attenuation of nitric oxide-mediated neuronal death. Previous studies have shown that global cerebral ischemia in rabbits impaired the subsequent acquisition of a trace-conditioned eyeblink reflex. Here, we examined the effect of preischemic treatment with lubeluzole on the acquisition of a trace-conditioned eyeblink response after 6.5 min of global cerebral ischemia. Three groups of rabbits underwent cerebral ischemia: one group underwent ischemia alone (I) and two groups underwent ischemia and also received lubeluzole (L1, 1.25 mg/kg, and L2, 2.5 mg/kg). All animals were subsequently trained using classical trace conditioning. Each training session consisted of the presentation of the conditioned stimulus (an 85-dB, 6-kHz auditory tone lasting for 100 ms) followed by a trace interval (a period of 300 ms during which no external stimulus was delivered) followed finally by the delivery of the unconditioned stimulus (a 150-ms puff of air directed at the cornea). We found that animals receiving preischemic administration of 1.25 mg/kg of lubeluzole demonstrated a significantly improved acquisition of the trace-conditioned reflex as compared to animals that did not receive lubeluzole. This finding demonstrates improved long-term neurobehavioral outcome with preischemic administration of 1.25 mg/kg of lubeluzole.

Original languageEnglish (US)
Pages (from-to)329-334
Number of pages6
JournalExperimental Brain Research
Volume152
Issue number3
DOIs
StatePublished - Oct 2003
Externally publishedYes

Fingerprint

lubeluzole
Brain Ischemia
Learning
Classical Conditioning
Ischemia
Rabbits
Sodium Channels
Calcium Channels
Cornea
Glutamic Acid
Nitric Oxide
Animal Models
Air

Keywords

  • Conditioning
  • Eyeblink
  • Global cerebral ischemia
  • Lubeluzole
  • Neuroprotection
  • Rabbits

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lubeluzole and conditioned learning after cerebral ischemia. / Mueller, Rashmi N.; Deyo, Donald J.; Brantley, David R.; Disterhoft, John F.; Zornow, Mark.

In: Experimental Brain Research, Vol. 152, No. 3, 10.2003, p. 329-334.

Research output: Contribution to journalArticle

Mueller, RN, Deyo, DJ, Brantley, DR, Disterhoft, JF & Zornow, M 2003, 'Lubeluzole and conditioned learning after cerebral ischemia', Experimental Brain Research, vol. 152, no. 3, pp. 329-334. https://doi.org/10.1007/s00221-003-1539-9
Mueller, Rashmi N. ; Deyo, Donald J. ; Brantley, David R. ; Disterhoft, John F. ; Zornow, Mark. / Lubeluzole and conditioned learning after cerebral ischemia. In: Experimental Brain Research. 2003 ; Vol. 152, No. 3. pp. 329-334.
@article{7160d597b28b4296a27c51f6ef8856ad,
title = "Lubeluzole and conditioned learning after cerebral ischemia",
abstract = "Lubeluzole [S-4-(2-benzothiazolylmethylamino)-α -((3,4-difluorophenoxy)methyl)-1-piperidineethanol] reduces the severity of cerebral injury in animal models of brain ischemia. Its beneficial effects may include decreased concentration of extracellular glutamate, blockade of sodium and calcium channels, and attenuation of nitric oxide-mediated neuronal death. Previous studies have shown that global cerebral ischemia in rabbits impaired the subsequent acquisition of a trace-conditioned eyeblink reflex. Here, we examined the effect of preischemic treatment with lubeluzole on the acquisition of a trace-conditioned eyeblink response after 6.5 min of global cerebral ischemia. Three groups of rabbits underwent cerebral ischemia: one group underwent ischemia alone (I) and two groups underwent ischemia and also received lubeluzole (L1, 1.25 mg/kg, and L2, 2.5 mg/kg). All animals were subsequently trained using classical trace conditioning. Each training session consisted of the presentation of the conditioned stimulus (an 85-dB, 6-kHz auditory tone lasting for 100 ms) followed by a trace interval (a period of 300 ms during which no external stimulus was delivered) followed finally by the delivery of the unconditioned stimulus (a 150-ms puff of air directed at the cornea). We found that animals receiving preischemic administration of 1.25 mg/kg of lubeluzole demonstrated a significantly improved acquisition of the trace-conditioned reflex as compared to animals that did not receive lubeluzole. This finding demonstrates improved long-term neurobehavioral outcome with preischemic administration of 1.25 mg/kg of lubeluzole.",
keywords = "Conditioning, Eyeblink, Global cerebral ischemia, Lubeluzole, Neuroprotection, Rabbits",
author = "Mueller, {Rashmi N.} and Deyo, {Donald J.} and Brantley, {David R.} and Disterhoft, {John F.} and Mark Zornow",
year = "2003",
month = "10",
doi = "10.1007/s00221-003-1539-9",
language = "English (US)",
volume = "152",
pages = "329--334",
journal = "Experimental Brain Research",
issn = "0014-4819",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Lubeluzole and conditioned learning after cerebral ischemia

AU - Mueller, Rashmi N.

AU - Deyo, Donald J.

AU - Brantley, David R.

AU - Disterhoft, John F.

AU - Zornow, Mark

PY - 2003/10

Y1 - 2003/10

N2 - Lubeluzole [S-4-(2-benzothiazolylmethylamino)-α -((3,4-difluorophenoxy)methyl)-1-piperidineethanol] reduces the severity of cerebral injury in animal models of brain ischemia. Its beneficial effects may include decreased concentration of extracellular glutamate, blockade of sodium and calcium channels, and attenuation of nitric oxide-mediated neuronal death. Previous studies have shown that global cerebral ischemia in rabbits impaired the subsequent acquisition of a trace-conditioned eyeblink reflex. Here, we examined the effect of preischemic treatment with lubeluzole on the acquisition of a trace-conditioned eyeblink response after 6.5 min of global cerebral ischemia. Three groups of rabbits underwent cerebral ischemia: one group underwent ischemia alone (I) and two groups underwent ischemia and also received lubeluzole (L1, 1.25 mg/kg, and L2, 2.5 mg/kg). All animals were subsequently trained using classical trace conditioning. Each training session consisted of the presentation of the conditioned stimulus (an 85-dB, 6-kHz auditory tone lasting for 100 ms) followed by a trace interval (a period of 300 ms during which no external stimulus was delivered) followed finally by the delivery of the unconditioned stimulus (a 150-ms puff of air directed at the cornea). We found that animals receiving preischemic administration of 1.25 mg/kg of lubeluzole demonstrated a significantly improved acquisition of the trace-conditioned reflex as compared to animals that did not receive lubeluzole. This finding demonstrates improved long-term neurobehavioral outcome with preischemic administration of 1.25 mg/kg of lubeluzole.

AB - Lubeluzole [S-4-(2-benzothiazolylmethylamino)-α -((3,4-difluorophenoxy)methyl)-1-piperidineethanol] reduces the severity of cerebral injury in animal models of brain ischemia. Its beneficial effects may include decreased concentration of extracellular glutamate, blockade of sodium and calcium channels, and attenuation of nitric oxide-mediated neuronal death. Previous studies have shown that global cerebral ischemia in rabbits impaired the subsequent acquisition of a trace-conditioned eyeblink reflex. Here, we examined the effect of preischemic treatment with lubeluzole on the acquisition of a trace-conditioned eyeblink response after 6.5 min of global cerebral ischemia. Three groups of rabbits underwent cerebral ischemia: one group underwent ischemia alone (I) and two groups underwent ischemia and also received lubeluzole (L1, 1.25 mg/kg, and L2, 2.5 mg/kg). All animals were subsequently trained using classical trace conditioning. Each training session consisted of the presentation of the conditioned stimulus (an 85-dB, 6-kHz auditory tone lasting for 100 ms) followed by a trace interval (a period of 300 ms during which no external stimulus was delivered) followed finally by the delivery of the unconditioned stimulus (a 150-ms puff of air directed at the cornea). We found that animals receiving preischemic administration of 1.25 mg/kg of lubeluzole demonstrated a significantly improved acquisition of the trace-conditioned reflex as compared to animals that did not receive lubeluzole. This finding demonstrates improved long-term neurobehavioral outcome with preischemic administration of 1.25 mg/kg of lubeluzole.

KW - Conditioning

KW - Eyeblink

KW - Global cerebral ischemia

KW - Lubeluzole

KW - Neuroprotection

KW - Rabbits

UR - http://www.scopus.com/inward/record.url?scp=0141452035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0141452035&partnerID=8YFLogxK

U2 - 10.1007/s00221-003-1539-9

DO - 10.1007/s00221-003-1539-9

M3 - Article

C2 - 12904938

AN - SCOPUS:0141452035

VL - 152

SP - 329

EP - 334

JO - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

IS - 3

ER -