SUBCHRONIC TREATMENT INCREASES THE DURATION OF THE COGNITIVE ENHANCEMENT INDUCED BY METRIFONATE

The study compared the efficacy of acute versus chronic metrifonate tr eatment to improve initial and reversal learning of the water maze spa tial navigation task in medial septal-lesioned rats. Acute oral admini stration of 30 mg/kg metrifonate at 30 min, but not at 150 or 360 min, before training improved the initial acquisition of the water maze ta sk. In contrast, improvement of initial learning performance of medial septal-lesioned rats pretreated for 21 days with metrifonate was obse rved irrespective of the timing of metrifonate treatment relative to b ehavioral testing. Reversal learning was assessed after a four-day was h-out period. No drug treatment was administered during this part of t he study. All the medial septal-lesioned rats that had received only a cute treatment with metrifonate during the initial learning stage were now as impaired as vehicle treated medial septal-lesioned rats. Howev er, the group subchronically pretreated with metrifonate performed bet ter than the vehicle-treated medial septal-lesioned controls. These re sults indicate that both acute and subchronic treatment with metrifona te can facilitate spatial learning in medial septal-lesioned rats and the transient nature of this beneficial effect after single acute admi nistration is transformed into a long-lasting improvement by subchroni c treatment. (C) 1997 Elsevier Science B.V.