Poster session: Chronic infusion of D,L-AP5 in a conditioned emotional response task

It is well established that N-methyl-D-aspartate (NMDA)-type glutamate receptors play an important role in learning and memory. Administration of the competitive NMDA antagonist 2-amino-5¬phosphonopentanoic acid (AP5) impairs hippocampus-dependent spatial learning, and learning of contextually, but not of auditory cued fear. Furthermore, AP5 inhibits hippocampal long-term potentiation of synaptic responses. However, a review of the data obtained in rodents reveals that timing and location of AP5 administration as well as the kind of test performed can markedly influence the effect of the drug. We have established a robust operant conditioning protocol for laboratory mice, which includes scheduled appetitive conditioning as well as acquisition and extinction of conditioned response suppression, and which allows us to investigate drug effects on different stages and kinds of learning. We have used this protocol to evaluate the effect of timing (pre and post conditioning), and duration (single or chronic) of drug administration in a dose-dependent manner. In the current study, we report the effect of chronic administration of AP5 on acquisition and extinction learning of fear¬related conditioned response suppression. Mini-osmotic pumps were implanted subcutaneously in C57/BI6 mice either before or after acquisition training, and two different concentrations of AP5 (25 mM and 100 mM) or vehicle were delivered via an intracerebroventricular catheter. Low and high doses of AP5 influenced performance of our mice quite differently, indicating that AP5 has complex effects on extinction learningstatus: publishe