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The protective effects of non-steroidal
anti-inflammatory drug treament in an animal model of Alzheimer's
disease. Ricky Lee Richardson, Eugene O'Hare, Eun-Mee Kim, Jim Cleary and Robert Adrian Shephard University of Ulster and Department of Veterans Affairs Medical Center, Northern Ireland and USA. Twenty five male rats were trained to respond in a two-lever operant apparatus under an alternating-lever cyclic-ratio schedule. Subjects were required to complete an ascending followed by a descending cycle of the ratio values 2, 6 12, 20, 30, 42 and 56 over six cycles, each response component being completed at the alternate lever to the last component. When responding showed no trends, subjects were divided into four groups. One group was injected bilaterally into the hippocampus with 5 ml sterile water and treated daily with 1.0 ml ibuprofen, one group was injected bilaterally into the hippocampus with 5.0 ml aggregated beta-amyloid (1-42) (Ab) suspension and daily received the vehicle in which ibuprofen was suspended, one group was injected bilaterally into the hippocampus with 5.0 ml aggregated Ab and was treated daily with 1.0 ml ibuprofen, and one group was injected bilaterally into the hippocampus with 5.0 ml aggregated Ab and treated daily with 1.0 ml ibuprofen but in this group ibuprofen treatment was withdrawn 62 days following Ab injection. The results show that daily treatment with ibuprofen protected against the effects of intrahippocampal injection of Ab, and that ibuprofen withdrawal produced a rapid deterioration toward the non-ibuprofen treated state. Keywords: Alzheimer's disease, ibuprofen, rat |
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