The development of antidepressants requires simple rodent behavioral tests for initial screening before undertaking more complex preclinical tests and clinical evaluation. Presented in the unit are two widely used screening tests used for antidepressants, the forced swim (also termed behavioral despair) test in the rat and mouse, and the tail suspension test in the mouse. These tests have good predictive validity and allow rapid and economical detection of substances with potential antidepressant‐like activity. The behavioral despair and the tail suspension tests are based on the same principle, measurement of the duration of immobility occurring following exposure of rodents to an inescapable situation. The majority of clinically used antidepressants decrease the duration of immobility. Testing of new substances in the behavioral despair and tail suspension tests allows a simple assessment of their potential antidepressant activity by the measurement of their effect on immobility. Curr. Protoc. Pharmacol. 38:5.8.1‐5.8.11. © 2007 by John Wiley & Sons, Inc.

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The f8-amyloid precursor protein (f8-APP), from which the .8-A4 peptide is derived, is considered to be central to the pathogenesis of Alzheimer disease (AD). Transgenic mice expressing the 751-amino acid isoform of human ,B-APP (f8-APP751) have been shown to develop early AD-like histopathology with diffuse deposits of f3-A4 and aberrant tau protein expression in the brain, particularly in the hippocampus, cortex, and amygdala. We now report that f8-APP751 transgenic mice exhibit age-dependent deficits in spatial learning in a water-maze task and in spontaneous alternation in a Y maze. These deficits were mild or absent in 6-month-old transgenic mice but were severe in 12-month-old transgenic mice compared to age-matched wild-type control mice. No other behavioral abnormalities were observed. These mice therefore model the progressive learning and memory impairment that is a cardinal feature of AD. These results provide evidence for a relationship between abnormal expression of ,f-APP and cognitive impairments.

These results demonstrate that the alpha7 receptor subtype is not involved in the effects of nicotine in the 5-CSRTT and that its effects are more likely to be mediated by a receptor(s) such as alpha4beta2, alpha4beta4 and/or alpha3beta2 which is sensitive to antagonism by dihydro-beta-erythroidine.

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