Comparison of the Effects of Antiepileptic Drugs (AEDs) on Short-Term Memory in Rats.
Abstract number :
1.271
Submission category :
Year :
2001
Submission ID :
160
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
H.E. Shannon, Neuroscience Division, Lilly Research Laboratories, Indianapolis, IN; P.L. Love, Neuroscience Division, Lilly Research Laboratories, Indianapolis, IN
RATIONALE: A potential undesirable side-effect of AEDs is cognitive disruption. However, there is relatively little information on potential animal models for predicting the potential to produce disruption or for investigating modes of action of AEDs in producing disruption. Spatial alternation behavior is a commonly used short-term memory test in rats which is highly sensitive to pharmacologic manipulation. Therefore, the purpose of the present studies was to compare the effects of several clinically useful AEDs on short-term memory as assessed by spatial alternation behavior in rats to determine if this test might be predictive of the potential of AEDs to produce cognitive disruption in humans.
METHODS: Rats were trained to respond alternately on the left and right levers in an operant conditioning chamber in order to obtain food pellets. The delay between trials was varied randomly between 2 and 32 sec. After behavior had stabilized, the percent correct responses decreased monotonically as the length of the delay was increased.
RESULTS: The percent correct responding was significantly decreased in a delay-dependent manner by carbamazepine, phenytoin, phenobarbital, valproate, topiramate, tiagabine and ethosuximide indicating that these AEDs had an adverse effect on short-term memory. The magnitude of the effects were similar to those produced by the benzodiazepine triazolam but less than those produced by the muscarinic receptor antagonist scopolamine. Lamotrigine produced effects which were not clearly dose-related. In contrast, levetiracetam and gabapentin were without significant effect on percent correct responding. Decreases in rates of responding were produced by carbamazepine, phenobarbital, valproate, tiagabine, ethosuximide, gabapentin and lamotrigine, but not by phenytoin or topiramate. Levetiracetam increased rates of responding.
CONCLUSIONS: The present findings in rats are similar to those obtained on cognition in normal volunteers. Thus, spatial alternation behavior may be a cognitive test in rats with predictive validity for the cognitive effects of AEDs in humans.
Support: Lilly Research Laboratories.
Disclosure: Salary - Employees of Eli Lilly and Company. Equity - HES has equity position in Eli Lilly and Company. Stock - HES has stock options from Eli Lilly and Company.