Working memory in the odor span task: effects of chlordiazepoxide, dizocilpine (MK801), morphine, and scopolamine.
BACKGROUND
A number of tasks are used to assess working memory in rodents, but the odor span task (OST) is unique in studying performance as a function of the number of stimuli to remember.


OBJECTIVE
The purpose of the present study was to better characterize the behavioral pharmacology of the OST by exploring the effects of several amnestic agents including an NMDA antagonist (dizocilpine), a positive GABA-A modulator (chlordiazepoxide), an anticholinergic compound (scopolamine), and as a negative control, an opiate receptor agonist (morphine).


METHODS
Rats were trained to perform on the OST which is a non-match-to-sample procedure with an incrementing number of sample odors to remember as the session progresses. Trials with a simple odor discrimination task (SD) were interspersed to provide a control for effects unrelated to memory load.


RESULTS
All four drugs disrupted performances on the OST task in a dose-dependent fashion, but only the NMDA antagonist dizocilpine produced impairments that were clearly dependent on the number of stimuli to remember. Dizocilpine impaired OST performance at a dose (0.1 mg/kg) that did not affect SD, and that impairment depended on memory load. Chlordiazepoxide (3.0 mg/kg) also produced amnestic effects that were manifest by shorter memory spans and runs of correct responding. In contrast, morphine and scopolamine impaired OST accuracy only at doses that also disrupted SD (18.0 and 0.3 mg/kg, respectively).


CONCLUSIONS
These results provide evidence of NMDA and benzodiazepine modulation of working memory as assessed by the OST.
University of North Carolina Wilmington, Wilmington, USA. galizio@uncw.edu
Mark
M
Galizio
Melissa
M
Deal
Andrew
A
Hawkey
Brooke
B
April
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D055696:Olfactory Perception / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology
D000701:Analgesics, Opioid; D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D018757:GABA Modulators; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002707:Chlordiazepoxide; D009020:Morphine; D012601:Scopolamine