Contextual fear conditioning and baseline startle responses in the rat fear-potentiated startle test: a comparison of benzodiazepine/gamma-aminobutyric acid-A receptor agonists

In the rat, fear-potentiated startle (FPS) test animals are first trained t o associate brief light presentations with a mild electric footshock and th en tested for startle responses to acoustic stimuli, delivered either in da rkness (i.e. baseline startle) or after the conditioning stimulus. Followin g light presentation the magnitude of the startle response is markedly incr eased, and the test is commonly used to distinguish anxiolytic drug effects (i.e. a reduction in FPS) from non-specific effects such as sedation / mus cle relaxation. However, recent studies suggest that the environment in whi ch the animal is trained may also contribute towards the acquisition of a c onditioned fear response (i.e. contextual fear conditioning) and that this may elevate startle responses recorded in the dark In the present study, th erefore, we have compared the benzodiazepine / gamma-aminobutyric acid-A re ceptor agonist chlordiazepoxide with the partial agonists FG 8205 and breta zenil, which are known to have a reduced propensity to produce sedation / m yorelaxation, using two different FPS procedures: (i) conditioning and test ing in stabilimeter chambers, and (ii) conditioning and testing in differen t environments, The results show that FPS can be demonstrated in both proce dures and that treatment with chlordiazepoxide, FG 8205 or bretazenil dose- dependently attenuates the response. However, animals conditioned and teste d in stabilimeter chambers also shelved a significant increase in dark-star tle amplitudes compared with non-shocked rats, suggesting that this respons e was elevated by contextual fear conditioning. Furthermore, despite clear differences in side-effect liabilities, FG 8205 and bretazenil significantl y reduced dark-startle responses, suggesting that this measure is also sens itive to the anxiolytic effects of benzodiazepines. In contrast, when anima ls were conditioned and tested in different environments, dark-startle resp onses were not significantly different from those recorded in non-shocked r ats and treatment with FG 8205 or bretazenil had no effect. Thus, condition ing and testing animals in different environments may provide a more effect ive means of distinguishing anxiolytic from non-specific drug effects in th e rat FPS test. (C) 2000 Lippincott Williams & Wilkins.