Behavioral perseveration and impairment of long-term memory in rats after intrahippocampal injection of kainic acid in subconvulsive dose

Delayed disturbances of cognitive functions caused by intrahippocampal injection of subconvulsive dose of kainic acid were studied in rats. Animals were behaviorally tested for the presence of cognitive deterioration 1 week after bilateral injection of 0.25 mu g kainic acid into the left and right hippocampi. Behavioral tests included the retrieval of a food-procuring task, its experimental extinction, and learning of a new similar task. Kainate-treated rats showed deterioration of performance of the task learned before the treatment: An impairment of the task performance occurred in the first trial of a daily session (each daily session consisted of 10 trials), and beginning from the second trial, the task was performed as rapidly as by control animals. This deterioration of retrieval in the first trial took place during several days, in spite of daily training during the retrieval test. Other disturbances of cognitive functions in kainate-treated rats were revealed in the test of experimental extinction of the response. At the initial step of this test, the rats showed active behavioral perseveration, performing habitual response with short latencies in spite of reinforcement removal. Besides, kainate-treated rats made significantly more responses before full extinction (inhibition of the previously learned response) than the control rats. In the learning test, kainate-treated rats did not exhibit any disturbances: repeated learning was the same as in the control group. Therefore, results showed that hippocampal dysfunctions induced by kainic acid resulted in the following cognitive disturbances: difficulties in memory retrieval and weakening of inhibitory control. These disturbances can be most adequately explained on the basis of the concept, according to which the hippocampus acts as a detector and comparator of new signals, thereby accomplishing selective attention. (C) 2007 Elsevier Inc. All rights reserved.