KETOGENIC DIET - EFFECTS ON EXPRESSION OF KINDLED SEIZURES AND BEHAVIOR IN ADULT RATS

Purpose: Despite use of the ketogenic diet (KD) for >75 years its effe ctiveness or mechanism of action has been examined in few animal studi es. Using the kindling model of epilepsy, we tested the anticonvulsant effectiveness and behavioral consequences of an experimental KD in ad ult rats. Methods: Rats fully kindled from the amygdala were divided i nto KD-fed or standard rat diet-fed groups; diet treatment continued f or 5 weeks. The KD approximated at 4:1 (''classic'') ketogenic diet an d consisted (by weight) of 70% fat, 14% protein, no carbohydrate, and appropriate vitamins, minerals and fiber; 92% of energy provided was c ontributed by fat and 8% was contributed by protein. Afterdischarge th reshold and duration (ADT, ADD) and stage 5 seizure threshold and dura tion (ST, SD) were assessed weekly for 5 weeks. During week 3, learnin g and memory were tested by the water maze and the behavioral response to a novel environment was assessed by the open field test. Results: Rats receiving the KD became ketonemic and had weight gains similar to those of control mts. As compared with rats receiving a standard diet , those fed the KD had an elevated ADT and ST for the first 2 weeks of treatment. The control and KD-fed groups did not differ with regard t o ADD or SD at any time during the study, and both groups performed si milarly in the water maze and open field test. Conclusions: In the kin dling model, the KD afforded transient protection against the focal ge neration of kindled seizures but not seizure spread. Rats that receive d the KD did not perform differently from control-fed rats on spatial learning or exploratory behavior tasks. Our results provide a promisin g model for study of the anticonvulsant mechanisms of ketosis.