Effects of pentobarbital and isoflurane on conditioned learning after transient global cerebral ischemia in rabbits

Abstract

Background: The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30°C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia. Methods: New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30°C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered. Results: Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group. Conclusions: This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.