D-cycloserine in prelimbic cortex reverses scopolamine-induced deficits in olfactory memory in rats

• Published in: PloS one Vol. 8; no. 8; p. e70584
• Main Authors: Portero-Tresserra, Marta, Cristóbal-Narváez, Paula, Martí-Nicolovius, Margarita, Guillazo-Blanch, Gemma, Vale-Martínez, Anna
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.08.2013; Public Library of Science (PLoS)
• Subjects: Acetylcholine receptors (muscarinic); Amino acids; Amnesia; Animal cognition; Animals; Antimetabolites - therapeutic use; Behavior, Animal - drug effects; Binding sites; Biology; Cognitive ability; Cortex (olfactory); Cycloserine; Cycloserine - therapeutic use; Drugs; Experiments; Flexibility; Food preferences; Food Preferences - drug effects; Glutamatergic transmission; Glutamic acid receptors (ionotropic); Glycine; Laboratory animals; Learning; Learning - drug effects; Limbic System - drug effects; Limbic System - metabolism; Male; Medicine; Memory; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - pathology; Memory tasks; Modulation; Muscarinic Antagonists - toxicity; N-Methyl-D-aspartic acid receptors; Neurotransmission; Odors; Olfactory Bulb - drug effects; Olfactory Bulb - physiology; Olfactory Bulb - surgery; Olfactory discrimination learning; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Rats; Rats, Wistar; Receptors; Reinforcement; Retention; Rodents; Scopolamine; Scopolamine - toxicity; Social and Behavioral Sciences; Social interactions; Studies
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0070584

A significant interaction between N-methyl-D-aspartate (NMDA) and muscarinic receptors has been suggested in the modulation of learning and memory processes. The present study further investigates this issue and explores whether d-cycloserine (DCS), a partial agonist at the glycine binding site of the NMDA receptors that has been regarded as a cognitive enhancer, would reverse scopolamine (SCOP)-induced amnesia in two olfactory learning tasks when administered into the prelimbic cortex (PLC). Thus, in experiment 1, DCS (10 µg/site) was infused prior to acquisition of odor discrimination (ODT) and social transmission of food preference (STFP), which have been previously characterized as paradigms sensitive to PLC muscarinic blockade. Immediately after learning such tasks, SCOP was injected (20 µg/site) and the effects of both drugs (alone and combined) were tested in 24-h retention tests. To assess whether DCS effects may depend on the difficulty of the task, in the STFP the rats expressed their food preference either in a standard two-choice test (experiment 1) or a more challenging three-choice test (experiment 2). The results showed that bilateral intra-PLC infusions of SCOP markedly disrupted the ODT and STFP memory tests. Additionally, infusions of DCS alone into the PLC enhanced ODT but not STFP retention. However, the DCS treatment reversed SCOP-induced memory deficits in both tasks, and this effect seemed more apparent in ODT and 3-choice STFP. Such results support the interaction between the glutamatergic and the cholinergic systems in the PLC in such a way that positive modulation of the NMDA receptor/channel, through activation of the glycine binding site, may compensate dysfunction of muscarinic neurotransmission involved in stimulus-reward and relational learning tasks.