Effects of Diazepam, Piracetam, and Mexidol on Passive Avoidance Response

Abstract

Effects of the anxiolytic diazepam and nootropics piracetam and mexidol on passive avoidance conditioning (PAC) in rats were compared in experiments using a three-compartment apparatus. The latter consisted of a central, brightly lit compartment, a noxious dark compartment in which footshock was delivered to a rat, and a safe dark compartment, where the rat was not exposed to electric shock. Footshock during the acquisition of passive avoidance response in the control animals caused an abrupt increase in the latency to escape from the central compartment during testing but did not result in preference for a safe compartment. On the basis of these data on differential effects of footshock on PAC, we suggested that learning processes, which determined the motor response delay and the safe compartment preference, had a diverse associative nature. An increase in latency is associated with the classical fear conditioning regardless of the place of electric shock exposure. In contrast to this, the safe compartment preference is associated with the formation of the memory trace about the location of the footshock exposure. The use of pharmacological substances that affect fear and memory in different ways provided additional arguments in favor of the assumption about various associative processes determining passive avoidance learning. Reduction in the level of fear using diazepam decreased the latency of motor response compared to the control value but did not affect the preference for a safe compartment. In contrast, the mnemotropic properties of piracetam and mexidol increased the preference for a safe compartment without increasing the latency. These differential pharmacological effects confirm that PAC is based on the fear conditioning, which causes an increase in the latency to escape from the central compartment, and on the memory of the location of shock exposure, which provides the preference for the safe compartment.