Anxiolytic Models

Elevated Plus Maze

The elevated plus-maze (EPM) has proven to be a valid and reliable test for the selective identification of anxiolytic and anxiogenic drug effects in both rats and mice. The EPM is composed of four arms with two different geometric characteristics, each differing from the others by the presence or absence of walls. Normal exploratory behavior in rats and mice is in the favor of the closed arms, and this tendency to stay in the closed arms of the maze can be enhanced by compounds that increase the aversion towards the anxiety-provoking open arms (i.e., anxiogenics). In contrast, administration of anxiolytic compounds reduces the natural aversion to the open arms and promotes the exploration thereof.

Light / Dark Box

The light/dark test is based on the innate aversion of rodents to brightly illuminated areas and on the spontaneous exploratory behavior of the animals, applying mild stressors (i.e., novel environment and light). A natural conflict situation occurs when an animal is exposed to an unfamiliar environment or novel objects. The conflict is between the tendency to explore and the initial tendency to avoid the unfamiliar (neophobia). The exploratory activity reflects the combined result of the tendencies in novel situations. Thus in the light/dark test drug induced increases in behavior in the white part of a 2 compartment box in which a large white compartment is illuminated and a small black compartment is darkened is suggested as an index of anxiolytic activity (Crawley and Goodwin, 1980).

Open-Field Test

The open field test (OFT) is a widely used procedure for examining the behavioral effects of drugs and anxiety. The OFT apparatus is composed of a large open field area with four walls. The natural tendency of rats when placed in the OFT apparatus is to remain in close contact with the walls, a behavior that is termed “thigmotaxis,” and avoid the large unknown and potentially dangerous open area. Test compounds that possess anxiolytic activity decrease the amount of time the rat spends in close proximity to the walls and increases exploratory activity in the center compartment.

Fear - Potential Startle

Fear-potentiated startle is the potentiation in acoustic startle response that occurs in rats when fear conditioned to associate an initially neutral stimulus and a potentially threatening stimulus. After a few pairings of these stimuli, the neutral stimulus becomes a conditioned stimulus, capable of eliciting behavioral fear responses. In rats, these responses include potentiation of startle reflex, and compounds that possess anxiolytic activity often oppose this potentiation in startle response.