Attentional Set‐Shifting Paradigm in the Rat

Piotr Popik1, Agnieszka Nikiforuk1

1 Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Kraków
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.51
DOI:  10.1002/0471142301.ns0951s72
Online Posting Date:  July, 2015
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The attentional set‐shifting task (ASST) is the rat version of the intra‐dimensional/extra‐dimensional (ID/ED) test and was developed fifteen years ago. Damage to the medial frontal cortex results in a failure to “unlearn” old contingencies, i.e., impairs ED set shifting. As such, the task measures cognitive flexibility that can be compromised both in schizophrenia and depression as well as in animal models of these diseases. © 2015 by John Wiley & Sons, Inc.

Keywords: cognition; cognitive flexibility; animal model; schizophrenia

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Table of Contents

  • Commentary
  • Figures
  • Tables
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Basic Protocol 1:

  • Male Sprague‐Dawley rats (weight: 200 to 250 g on arrival)
  • Flavoring essence (e.g., Dr. Oetker; see Table 9.51.1)
  • Media (i.e., inexpensive small materials to cover bait placed on the bottom of ceramic pots; see Table 9.51.1)
  • Honey Nut Cheerios (Nestlé)
  • Drugs and compounds
  • Custom‐made Plexiglas apparatus
    • Length × width × height: 70 × 40 × 20 cm; with grid floor and removable divider that divides the box into two equally sized sections: start box and choice area (see Fig. )
  • Ceramic pots
  • Video camera and monitor
  • Blotting paper
  • Adhesive tape
NOTE: Male Sprague‐Dawley rats are housed in a temperature‐controlled (21 ± 1°C) and humidity‐controlled (40% to 50%) colony room under a 12 hr/12 hr light/dark cycle (lights on at 06:00 hr). Rats should be mildly food restricted (17 g of food pellets per day) for at least 1 week prior to testing. Behavioral testing is performed during the light phase of the light/dark cycle. In our experimental setting, rats are housed individually. To avoid prolonged isolation in long‐term experiments, pair‐ or group‐housed rats can also be employed (e.g., Tait et al., ).NOTE: Apply the flavoring essence to a piece of blotting paper and fix it to the internal rim of the pot immediately prior to use (see arrows in Figure ).NOTE: Food reward/bait: Other authors use Froot Loops (Kellogg's) or Chocapic (Nestlé).NOTE: During testing, one ceramic digging pot (internal diameter: 10.5 cm and depth: 4 cm) is placed in each section of the apparatus. Various investigators use different pots (containers). Since tens of different pots are necessary, an inexpensive solution is to purchase 50 identical ashtrays. Each pot is defined by a pair of cues along with two stimulus dimensions: the odor and the medium (Fig. ).NOTE: Use a different pot for each combination of digging medium and odor; only one odor should ever be applied to a given pot. Note that neither the media nor the odors used in the given discrimination phase should differ too much from each other; they should also not be too similar, and should not be aversive for the rats. Do not use odors that are too similar to each other (e.g., lemon and orange). Do not use odors from different manufacturers differing significantly in their physical properties (e.g., intensity). Do a pilot discrimination for pairs of media and pairs of odors before the main experiment.
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Literature Cited

Literature Cited
  Berg, E.A. 1948. A simple objective technique for measuring flexibility in thinking. J. Gen. Psychol. 39:15‐22.
  Birrell, J.M. and Brown, V.J. 2000. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J. Neurosci. 20:4320‐4324.
  Brooks, J.M., Pershing, M.L., Thomsen, M.S., Mikkelsen, J.D., Sarter, M., and Bruno, J.P. 2012. Transient inactivation of the neonatal ventral hippocampus impairs attentional set‐shifting behavior: Reversal with an α7 nicotinic agonist. Neuropsychopharmacology 37:2476‐2486.
  Dias, R., Robbins, T.W., and Roberts, A.C. 1996. Primate analogue of the Wisconsin Card Sorting Test: Effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav. Neurosci. 110:872‐886.
  Dias, R., Robbins, T.W., and Roberts, A.C. 1997. Dissociable forms of inhibitory control within prefrontal cortex with an analog of the Wisconsin Card Sort Test: Restriction to novel situations and independence from “on‐line” processing. J. Neurosci. 17:9285‐9297.
  Egerton, A., Reid, L., McGregor, S., Cochran, S.M., Morris, B.J., and Pratt, J.A. 2008. Subchronic and chronic PCP treatment produces temporally distinct deficits in attentional set shifting and prepulse inhibition in rats. Psychopharmacology 198:37‐49.
  Featherstone, R.E., Rizos, Z., Nobrega, J.N., Kapur, S., and Fletcher, P.J. 2007. Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: Parallels to schizophrenia. Neuropsychopharmacology 32:483‐492.
  Floresco, S.B., Zhang, Y., and Enomoto, T. 2009. Neural circuits subserving behavioral flexibility and their relevance to schizophrenia. Behav. Brain Res. 204:396‐409.
  Fossati, P., Amar, G., Raoux, N., Ergis, A.M., and Allilaire, J.F. 1999. Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia. Psychiatry Res. 89:171‐187.
  Goetghebeur, P. and Dias, R. 2009. Comparison of haloperidol, risperidone, sertindole, and modafinil to reverse an attentional set‐shifting impairment following subchronic PCP administration in the rat—a back translational study. Psychopharmacology 202:287‐293.
  Goetghebeur, P.J. and Dias, R. 2014. The attentional set‐shifting test paradigm in rats for the screening of novel pro‐cognitive compounds with relevance for cognitive deficits in schizophrenia. Curr. Pharm. Des. 20:5060‐5068.
  Grant, D.A. and Berg, E.A. 1948. A behavioral analysis of degree of reinforcement and ease of shifting to new responses in a Weigl‐type card‐sorting problem. J. Exp. Psychol. 38:404‐411.
  Lapiz‐Bluhm, M.D., Bondi, C.O., Doyen, J., Rodriguez, G., Bedard‐Arana, T., and Morilak, D.A. 2008. Behavioural assays to model cognitive and affective dimensions of depression and anxiety in rats. J. Neuroendocrinol. 20:1115‐1137.
  McAlonan, K. and Brown, V.J. 2003. Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behav. Brain Res. 146:97‐103.
  McLean, S.L., Beck, J.P., Woolley, M.L., and Neill, J.C. 2008. A preliminary investigation into the effects of antipsychotics on sub‐chronic phencyclidine‐induced deficits in attentional set‐shifting in female rats. Behav. Brain Res. 189:152‐158.
  Nikiforuk, A. and Popik, P. 2011. Long‐lasting cognitive deficit induced by stress is alleviated by acute administration of antidepressants. Psychoneuroendocrinology 36:28‐39.
  Preuss, T.M. 1995. Do rats have prefrontal cortex? The Rose‐Woolsey‐Akert program reconsidered. J. Cogn. Neurosci. 7:1‐24.
  Roberts, A.C., Robbins, T.W., Everitt, B.J., and Muir, J.L. 1992. A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets. Neuroscience 47:251‐264.
  Rodefer, J.S., Nguyen, T.N., Karlsson, J.J., and Arnt, J. 2008. Reversal of subchronic PCP‐induced deficits in attentional set shifting in rats by sertindole and a 5‐HT6 receptor antagonist: Comparison among antipsychotics. Neuropsychopharmacology 33:2657‐2666.
  Tait, D.S., Marston, H.M., Shahid, M., and Brown, V.J. 2009. Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions. Psychopharmacology 202:295‐306.
  Tollefson, G.D. 1996. Cognitive function in schizophrenic patients. J. Clin. Psychiatry 57:31‐39.
Key References
  Birrell, J.M. and Brown, V.J. 2000. Medial frontal cortex mediates perceptual attentional set shifting in the rat. J. Neurosci. 20:4320‐4324.
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