Optimization and robustness of the inhibitory avoidance test for pharmacological screening on long-term memory

One of the challenges in pharmacological screening is to maximize the throughput of tests in order to evaluate the potential efficacy of a large number of compounds in a minimal amount of time. The inhibitory avoidance test, also called passive avoidance, has long been used as a screening test to evaluate drug effects on the memory in rodents [1,2]. The test is based on the natural photophobia of mice or rats, and evaluates the long-term memory of animals. The apparatus (Ugo Basile, see picture below) consists of a box divided into two compartments of equal sizes (18x10x16 cm) and equipped with a grid floor. One compartment is made of white panels, and illuminated with a lamp placed on the top of the chamber (≈ 350 lux). The other compartment is made of black panels (≈4 lux). The two compartments are separated by a guillotine door. In a typical trial (acquisition trial), the animal is placed in the bright compartment and readily enters the dark compartment. At that moment, the door separating the two compartments automatically closes, and the animal receives a brief mild electric shock (0.3mA-3s). During a subsequent trial (retention trial), the latency to enter the dark compartment is recorded as an index of memory consolidation. The longer the latency to enter the dark compartment, the better the animal is supposed to remember it received an electric shock during a previous trial [3].