Effects of hypothermia and lamotrigine on trace-conditioned learning after global cerebral ischemia in rabbits

Jae Young Kwon, Andreas Bacher, Donald J. Deyo, Marjorie R. Grafe, John F. Disterhoft, Tatsuo Uchida, Mark H. Zornow

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Acquisition of the trace-conditioned eye blink response (CR) is mediated by a variety of brain structures, including the cerebellum, the hippocampus, and brain stem nuclei. We examined the effects of a neuronal sodium channel antagonist (lamotrigine) on the ability of rabbits to acquire an eye blink CR after 6.5 min of cerebral ischemia. New Zealand white rabbits (n = 31) were randomly assigned to sham (S), normothermic ischemia (N), hypothermic (30°C) ischemia(H), or lamotrigine (50 mg/kg) treated (L) groups. In the N, H, and L groups, 6.5 min of global cerebral ischemia was produced using an inflatable neck tourniquet. Trace conditioning was started on the 7th postischemic day. The conditioned stimulus consisted of a tone (85 dB, 6 kHz) presented for 100 ms. The unconditioned stimulus was an air puff (150 ms duration) directed at the cornea. The interval between the end of the conditioned stimulus and the start of the unconditioned stimulus (the trace interval, TI) was 300 ms in duration. A trace-conditioned response was defined as an eye blink that was initiated during the TI. Eighty trials were delivered daily for 15 days. Neurologic deficits were greatest in the N group, and these animals had fewer CRs (149 ± 157) than animals in the S (509 ± 214) or H (461 ± 149) groups (P < 0.05 by analysis of variance). Animals in the L group had a total number of CRs (380 ± 253) that was intermediate between the S and N groups. Histologic evidence of neural injury was greatest in the N group. This study demonstrates that a brief episode of cerebral ischemia results in the impairment of this test of neurobehavioral function. Both hypothermia and lamotrigine were able to attenuate the impairment of eye blink trace- conditioned responses produced by cerebral ischemia.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalExperimental Neurology
Issue number1
StatePublished - Sep 1999
Externally publishedYes


  • Brain
  • Conditioned response
  • Hypothermia
  • Ischemia
  • Lamotrigine
  • Rabbits

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience


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