title: Influence of pharmacological manipulations of NMDA and cholinergic receptors on working versus reference memory in a dual component odor span task.
abstract: Developed as a tool to assess working memory capacity in rodents, the odor span task (OST) has significant potential to advance drug discovery in animal models of psychiatric disorders. Prior investigations indicate OST performance is impaired by systemic administration of N-methyl-d-aspartate receptor (NMDA-r) antagonists and is sensitive to cholinergic manipulations. The present study sought to determine whether an impairment in OST performance can be produced by systemic administration of the competitive NMDA-r antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP; 3, 10, 17 mg/kg i.p.) in a unique dual-component variant of the OST, and whether this impairment is ameliorated by nicotine (0.75 mg/kg i.p.). Male Sprague-Dawley rats were trained to asymptotic level of performance on a 24-trial two-comparison incrementing nonmatching to sample OST. In addition, rats were administered a two-comparison olfactory reference memory (RM) task, which was integrated into the OST. The RM task provided an assessment of the effects of drug administration on global behavioral measures, long-term memory and motivation. Several measures of working memory (span, longest run, and accuracy) were dose dependently impaired by CPP without adversely affecting RM. Analysis of drug effects across trial blocks demonstrated a significant impairment of performance even at low memory loads, suggesting a CPP-induced deficit of olfactory short-term memory that is not load-dependent. Although nicotine did not ameliorate CPP-induced impairments in span or accuracy, it did block the impairment in longest run produced by the 10 mg/kg dose of CPP. Overall, our results indicate that performance in our 24 odor two-comparison OST is capacity dependent and that CPP impaired OST working, but not reference, memory.
authors.affiliation: Moffitt Cancer Center, Tampa, Florida 33612, USA Department of Psychology, University of South Florida, Tampa, Florida 33620, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: MacQueen
authors.affiliation: Medical Research Service, VA Hospital, Tampa, Florida 33612, USA Department of Psychology, University of South Florida, Tampa, Florida 33620, USA.
authors.forename: Savannah R
authors.initials: SR
authors.lastname: Dalrymple
authors.affiliation: Moffitt Cancer Center, Tampa, Florida 33612, USA Department of Psychology, University of South Florida, Tampa, Florida 33620, USA Department of Oncologic Sciences, University of South Florida, Tampa, Florida 33620, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Drobes
authors.affiliation: Medical Research Service, VA Hospital, Tampa, Florida 33612, USA Department of Psychology, University of South Florida, Tampa, Florida 33620, USA Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida 33620, USA Center for Preclinical and Clinical Research on PTSD, University of South Florida, Tampa, Florida 33620, USA ddiamond@mail.usf.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Diamond
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009042:Motivation / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D009812:Odorants; D055696:Olfactory Perception / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D011978:Receptors, Nicotinic
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D009538:Nicotine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid