ARECOLINE VIA MINIOSMOTIC PUMP IMPROVES AF64A-IMPAIRED RADIAL MAZE PERFORMANCE IN RATS - A POSSIBLE MODEL OF ALZHEIMERS-DISEASE

Male Sprague-Dawley rats, preoperatively trained in a I-h delay non-ma tch-to-position radial maze task, received bilateral stereotaxic injec tions of a selective cholinotoxin, ethylcholine aziridinium ion (AF64A : 3 nmol/3 mu l/lateral ventricle). Animals treated with AF64A made si gnificantly more total postdelay errors than vehicle controls. Sustain ed delivery, via miniosmotic pumps, of arecoline (0.1, 0.3, 1, 3, 10, or 30 mg/kg/day sc for 14 days) attenuated the AF64A-induced cognitive impairment in a dose-dependent manner, producing an inverted U-shaped dose-response function which was optimal at 1.0 mg/kg/day. Following these studies, choline acetyltransferase activity was significantly re duced in hippocampi extracted from the AF64A-treated rats, indicating successful cholinotoxicity. This paradigm may be useful as a possible screen for potential Alzheimer's disease therapeutic agents. This conc lusion is supported by published reports of beneficial arecoline effec ts observed following 2-week intravenous infusions in patients with Al zheimer's disease (Soncrant, Raffaele, Asthana, Berardi, Morris, & Hax by, 1993). (C) 1997 Academic Press.