Models of Dementia: Delayed Alternation in Aged Rats

Sylvian Roux1, Isabelle Hubert1, Roger D. Porsolt1

1 Phoenix International Pharmacology, Le Kremlin‐Bicêtre, France
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.13
DOI:  10.1002/0471141755.ph0513s02
Online Posting Date:  May, 2001
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Abstract

Operant delayed alternation tasks are useful tools for assessing age‐related memory deficits in rats. Decreased accuracy in these tasks seems to reflect mainly an inability to remember and utilize recent events (short‐term memory deficit). The task described in this unit requires the rat to learn a delayed alternation for food reward in a standard Skinner box, so it must retain spatial information over a short period of time. Aged rats exhibit clear short‐term memory impairments (decrease in response accuracy) in the task compared to young rats during learning and later, after extended training, also exhibit performance deficits. An advantage of studying these two phases is the possibility to examine either chronic effects (repeated drug administrations during acquisition) or acute effects (single treatments given before the test session during the stabilized performance phase). Operant delayed alternation tasks are useful tools for assessing age‐related memory deficits in rats

     
 
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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Acquisition of an Operant Delayed Alternation Task in Young and Aged Rats
  • Alternate Protocol 1: Stabilized Performance of an Operant Delayed Alternation Task in Young and Aged Rats
  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: Acquisition of an Operant Delayed Alternation Task in Young and Aged Rats

  Materials
  • Male Wistar rats, 2 to 3 months old (200 to 250 g at beginning of experiment) and 20 to 22 months old (500 to 750 g at beginning of experiment)
  • Test compounds (see recipe)
  • Physiological saline: 0.9% NaCl, sterile
  • 33 × 21 × 18–cm transparent Macrolon cages equipped with wood shavings
  • Sound‐attenuated, ventilated standard Skinner boxes (30 × 25 × 30–cm; Model E10.10, Coulbourn Instruments) fitted with a white houselight situated directly above a food receptacle connected to a pellet dispenser for 45‐mg pellets
  • 45‐mg food pellets (Bioserv)
  • Retractable levers for Skinner boxes (Coulbourn Instruments; 2 per box)
  • IBM‐compatible computer equipped with MED‐PC programming system and MED hardware interface (MED Associates)
  • Sartorius balance (type 1401.001.2; accuracy 1 g)
  • Terumo syringes, type B5‐05S, and Terumo needles, 25‐G × 5/8 in. (0.5 × 16–mm), for intraperitoneal and subcutaneous administration of test substances or luer gastric probes with olive extremity (25 mm × 12/10 mm) for oral administration

Alternate Protocol 1: Stabilized Performance of an Operant Delayed Alternation Task in Young and Aged Rats

  • Male Wistar rats: 4 to 8 months old (300 to 350 g) and 22 to 26 months old (450 to 650 g)
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Figures

Videos

Literature Cited

Literature Cited
   Bartus, R. and Dean, R.L. 1985. Developing and utilizing animal models in the search for an effective treatment for age‐related memory disturbances. In Normal Alzheimer's Disease and Senile Dementia: Aspects of Etiology, Pathogenesis, Diagnosis and Treatment. (C.G. Gottfries, ed.) pp. 231‐267. EVB, Brussels.
   Bartus, R.T., Flicker, C., and Dean, R.L. 1983. Logical principles for the development of animal models of age‐related memory impairments. In Assessment in Geriatric Psychopharmacology. (T. Crook, R.T. Bartus, S. Ferris, and S. Gershon, eds.) pp. 263‐299. Mark Powley Associates, Madison, Conn.
   Buccafusco, J.J. and Jackson, W.J. 1991. Beneficial effects of nicotine administered prior to a delayed matching‐to‐sample task in young and aged monkeys. Neurobiol. Aging 12:233‐238.
   Dunnett, S.B., Evenden, J.L., and Iversen, S.D. 1988. Delay‐dependent short‐term memory deficits in aged rats. Psychopharmacology 96:174‐180.
   Moore, H., Dudchenko, P., Bruno, J.P., and Sarter, M. 1992. Toward modeling age‐related changes of attentional abilities in rats: Simple and choice reaction time tasks and vigilance. Neurobiol. Aging 13:759‐772.
  Olton, D.S. 1993. Age‐related behavioral impairments: Benefits of multiple measures of performance. Neurobiol. Aging 14:637‐638.
  Porsolt, R.D., Roux, S., and Wettstein, J.G. 1995. Animal models of dementia. Drug Dev. Res. 35:214‐229.
  Roux, S., Hubert, I., Leneègre, A., Milinkevitch, D., and Porsolt, R.D. 1994. Effects of piracetam on indices of cognitive function in a delayed alternation task in young and aged rats. Pharmacol. Biochem. Behav. 49:683‐688.
   Roux, S., Hubert, I., Wettstein, J.G., Soubrié, S., Le Fur, G., and Porsolt, R.D. 1995. Facilitating effects of SR 57746 A on short‐term memory in an operant delayed alternation task in aged rats. Drug Dev. Res. 35:83‐93.
   Sahakian, B.J., Owen, A.M., Morant, N.J., Eagger, S.A., Baddington, S., Crayton, L., Crockford, H.A., Crooks, M., Hill, K., and Levy, R. 1993. Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: Assessment of attentional and mnemonic function using CANTAB. Psychopharmacology 110:395‐401.
   Sarter, M. 1987. Measurement of cognitive abilities in senescent animals. Int. J. Neurosci. 32:765‐774.
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