Two phases of behavioral plasticity in rats following unilateral excitotoxic lesion of the hippocampus

We investigated the effects of dizocilpine, a non-competitive N-methyl-D-as partate receptor antagonist, on spatial reference and working memory in a r adial arm maze task in rats with a unilateral hippocampal lesion. At a dose of 0.2 mg/kg to intact rats, dizocilpine significantly impaired both refer ence and working memory, and produced ataxia and impairment of food intake; at 0.1 mg/kg, dizocilpine had no effect on performance. Unilateral hippoca mpal lesion induced by quinolinic acid produced a marked working memory def icit concomitant with a slight but significant impairment of reference memo ry when mnemonic ability was examined one week after the lesion. The spatia l memory deficits in the rats with a unilateral hippocampal lesion were ame liorated by repeated daily trainings over a 21-day period. Following recove ry of the spatial memory deficits produced by the brain lesion (four weeks after the brain lesion), dizocilpine (0.1 mg/kg) significantly impaired bot h reference and working memory, without affecting general behavior or food intake in the brain-lesioned rats. An impairment of working memory, but not reference memory, by dizocilpine was observed six weeks after the brain le sion. However, the disrupting effect of dizocilpine at 0.1 mg/kg on spatial working memory had disappeared at eight weeks after the lesion. Ten weeks after the brain lesion, dizocilpine at 0.2 mg/kg was necessary to induce sp atial memory impairment, which was accompanied by motor and food intake def icits, as in intact rats. In sham-operated rats, the dose-response effects of dizocilpine did not differ from those in intact rats at any time after t he operation. These results suggest that two phases of behavioral plasticity take place, depending on demand, to compensate for brain dysfunction after the unilater al lesion of the hippocampus in rats. (C) 1999 IBRO. Published by Elsevier Science Ltd.