Evaluation of two rodent delayed-response memory tasks: a method with retractable levers versus a method with closing doors.
The purpose of this study was to evaluate and compare two similar rodent memory tasks developed in our laboratory that employ stimulus discrimination and delayed response (light and tone stimuli and variable length delays) and to determine their sensitivity to the muscarinic-acetylcholine receptor (mAChR) antagonist, scopolamine hydrobromide (SCOP HBr), and its quaternary (methylbromide) analog (SCOP MBr). Male Wistar rats were trained in either an open chamber that employed retracting levers (RLM) during the delays, or a method that utilized closing doors (CDM) that separated the rats from the levers during delays to reduce positional (nonmnemonic) strategies. When the rats were well trained, dose-effect studies (microg/kg doses, s.c., 30 min before test sessions) of SCOP HBr or MBr were performed. Baseline performance was characterized by delay-dependent decreases in accuracy in both methods except when the tone was the stimulus in the RLM. SCOP HBr impaired performance in both tasks at the higher doses tested, although the effects were more consistent in the CDM task and accuracy associated with each stimulus was affected similarly. Surprisingly, SCOP MBr also impaired performance of each task, especially when the tone was the stimulus, while accuracy associated with the light was not affected in the CDM task. Overall, the results indicated that the CDM was a somewhat more reliable task, appearing to reduce positional strategies with less variability in response to the mAChR antagonists, although some stimulus-modality specific effects were noted. It also appears important to consider the peripheral effects of mAChR antagonists (and potential central effects of quaternary mAChR antagonists) when interpreting results from behavioral studies, especially those involving conditional discrimination and delayed response.
Evans-Martin
F F
FF
Department of Pharmacology and Toxicology, Alzheimer's Research Center, Medical College of Georgia, CJ-1020, Augusta, GA 30912 USA.
Terry
A V
AV
Jackson
W J
WJ
Buccafusco
J J
JJ
D000161:Acoustic Stimulation; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
D018727:Muscarinic Antagonists; D012601:Scopolamine