Models of Neurological Disease (Alzheimer's Disease): Spatial Discrimination Water Maze Test in Septal‐Lesioned Rats

Michael W. Decker1

1 Abbott Laboratories, Abbott Park, Illinois
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.14
DOI:  10.1002/0471141755.ph0514s03
Online Posting Date:  August, 2001
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

Models of Alzheimer s disease currently focus on symptomatology, as understanding of the etiology of the disorder is not yet sufficiently advanced to model the disease process in animals. Moreover, currently available treatments are purely palliative in nature. Given that cognitive dysfunction is a central feature of the disease, animal models of cognitive dysfunction are frequently used to evaluate the therapeutic potential of test compounds. This unit presents a rat model in which a brain lesion is produced which disrupts septohippocampal function, thus impairing performance on a spatial learning task (the Morris water maze).

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Basic Protocol 1: Assessment of Spatial Discrimination in Septal‐Lesioned Rats Using the Morris Water Maze
  • Commentary
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

Basic Protocol 1: Assessment of Spatial Discrimination in Septal‐Lesioned Rats Using the Morris Water Maze

  Materials
  • Rats (preferably Long‐Evans or other pigmented strain, ∼250 g)
  • Sodium pentobarbital (e.g., Abbott Labs) or other anesthetic
  • 1‐ml syringe with 27‐G needle
  • Powdered milk sufficient to make the water in the tank opaque
  • Nissl stain
  • Hair clippers
  • Povidone/iodine solution
  • Stereotactic frame and electrode carrier
  • Scalpel
  • Cotton‐tip applicators
  • Dental drill or hobby drill with 2‐mm or 3/32‐inch bit
  • Dental pick or dissecting pin
  • Radiofrequency lesion maker (e.g., RFG‐4A lesion maker; Radionics)
  • Lesion electrode (0.7‐mm diameter, 1.5‐mm tip exposure)
  • Gelfoam (Pharmacia & Upjohn)
  • 9‐mm wound clips and applicator
  • Warming plate set at 37°C
  • Large round water tank ∼180 cm in diameter and 60 cm high (Fig. see step for construction details)
  • 1 round piece of PVC tubing ∼35 cm long and 13 cm in diameter
  • Hardware cloth or other material to cover one end of tube
  • 4 fittings designed to hold the PVC tubing (to be anchored to the water tank floor)
  • Circular piece of expanded polystyrene 13 cm in diameter and ∼1.5 cm thick
  • Fishing line
  • Weight for anchoring floating platform
  • Source of hot water for adjusting tank water temperature
  • Stopwatch
  • Video monitoring system (optional)
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Bannon, A.W., Curzon, P., Gunther, K.L., and Decker, M.W. 1996. Effects of intraseptal injection of 192‐IgG‐saporin on spatial learning in mature and aged rats. Brain Res. 718:25‐36.
   Brioni, J.D., Curzon, P., Buckley, M.J., Arneric, S.P., and Decker, M.W. 1993. Linopirdine (DuP996) facilitates the retention of avoidance training and improves performance of septal‐lesioned rats in the water maze. Pharmacol. Biochem. Behav. 44:37‐43.
   Bures, J., Buresova, O., and Huston, J. 1983. Techniques and Basic Experiments for the Study of Brain and Behavior. Elsevier Science Publishers, Amsterdam.
   Decker, M.W. 1995. Animal models of cognition. Crit. Rev. Neurobiol. 9:321‐343.
   Decker, M.W., Radek, R.J., Majchrzak, M.J., and Anderson, D.J. 1992a. Differential effects of medial septal lesions on spatial‐memory tasks. Psychobiology 20:9‐17.
   Decker, M.W., Majchrzak, M.J., and Anderson, D.J. 1992b. Effects of nicotine on spatial memory deficits in rats with septal lesions. Brain Res. 572:281‐285.
   Decker, M.W., Majchrzak, M.J., and Arneric, S.P. 1993. Effects of lobeline, a nicotinic receptor agonist, on learning and memory. Pharmacol. Biochem. Behav. 45:571‐576.
   Decker, M.W., Curzon, P., and Brioni, J.D. 1995. Influence of separate and combined septal and amygdala lesions on memory, acoustic startle, anxiety, and locomotor activity in rats. Neurobiol. Learn. Mem. 64:156‐168.
   Fonnum, F. 1975. A rapid radiochemical method for the determination of choline acetyltransferase. J. Neurochem. 24:407‐409.
   Fried, P.A. 1973. The septum and hyper‐reactivity: A review. Br. J. Psychol. 64:267‐275.
   Gallagher, M., and Colombo, P.J. 1995. Ageing: The cholinergic hypothesis of cognitive decline. Cur. Opin. Neurobiol. 5:161‐168.
   Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F. et al., 1995. Alzheimer‐type neuropathology in transgenic mice overexpressing V717F β‐amyloid precursor protein. Nature 373:523‐527.
   Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., and Cole, G. 1996. Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274:99‐102.
   Moran, P.M., Higgins, L.S., Cordell, B., and Moser, P.C. 1995. Age‐related learning deficits in transgenic mice expressing the 751‐amino acid isoform of human β‐amyloid precursor protein. Proc. Natl. Acad. Sci. U.S.A. 92:5341‐5345.
   Morris, R.G.M. 1981. Spatial localization does not require the presence of local cues. Learn. Motiv. 12:239‐260.
   Sarter, M., Hagan, J., and Dudchenko, P. 1992a. Behavioral screening for cognition enhancers: From indiscriminate to valid testing: Part I. Psychopharmacology 107:144‐159.
   Sarter, M., Hagan, J., and Dudchenko, P. 1992b. Behavioral screening for cognition enhancers: From indiscriminate to valid testing: Part II. Psychopharmacology 107:461‐473.
Key References
   Morris, 1981. See above.
  Provides the original description of the Morris water maze.
   O'Keefe, J., and Nadel, L. 1978. The Hippocampus as a Cognitive Map. Clarendon Press, Oxford.
  Advances the hypothesis that the hippocampus plays a special role in spatial learning.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library