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Cognitive effects of psychotomimetic drugs in rats discriminating number cues

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Abstract

Rationale

Deficits in memory and attention are broadly acknowledged during psychosis; however, experiments on modeled psychosis often test working memory without systematic manipulation of attentional demands.

Objectives

The major research goal was discovering which neurobehavioral processes, attention, or memory contributed more to drug-provoked performance deficits.

Materials and methods

Rats were trained to perform operant ratio discrimination (RD) tasks wherein the number of presses at a rear-wall lever was discriminated using one of two front-wall levers. Effects from four psychotomimetic drugs, the serotonin agonist 2,5-dimethoxy-4-iodoamphetamine, the noncompetitive NMDA-glutamate receptor antagonist phencyclidine (PCP), and two CB1-selective cannabinoid agonists, WIN 55,512-2 and AM 411, were assessed using a signal detection analytical overlay to dissociate cognitive from noncognitive motor and motivational disruptions. Further methods allowed dissociation of attention compromises from mnemonic deficits.

Results

For each test compound, at least one dose elicited decreased RD accuracy without affecting response rates, and task difficulty was shown to be a crucial dictator of accuracy effect specificities. Effects from both PCP and WIN 55,512-2 biased animals to select the response lever conditioned for denser reinforcement. The same two drugs rendered peculiar response patterns in distracter light session components, considering light blinks were included to divert subjects’ attention away from task-relevant information. The response patterns determined during distracter components of PCP/WIN testing sessions, counterintuitively, suggest performance enhancement.

Conclusion

Comprehensive viewing of RD performance patterns after drug administration indicates that sustained attention and transient information management are significantly impaired during the drug-induced psychosis state, while selective attention is less affected.

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Authors and Affiliations

  1. Raabe College of Pharmacy, Ohio Northern University, Ada, OH, 45810, USA

    C. B. Willmore & D. M. Krall

  2. University of Maryland School of Pharmacy, Baltimore, MD, 21201, USA

    C. B. Willmore

  3. Harding University College of Pharmacy, Searcy, AR, 72149, USA

    C. B. Willmore & F. M. Spears

  4. Center for Drug Discovery, Northeastern University, Boston, MA, USA

    A. Makriyannis

  5. Department of Psychiatry, University of Maryland School of Medicine; Maryland Psychiatric Research Institute, Baltimore, MD, USA

    G. I. Elmer

Authors
  1. C. B. Willmore
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  2. D. M. Krall
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  3. F. M. Spears
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  4. A. Makriyannis
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  5. G. I. Elmer
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Corresponding author

Correspondence to C. B. Willmore.

Additional information

The authors extend thanks to J. Edward Moreton, Ph.D., for the University of Maryland School of Pharmacy, for technical and conceptual contributions to this research effort.

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Willmore, C.B., Krall, D.M., Spears, F.M. et al. Cognitive effects of psychotomimetic drugs in rats discriminating number cues. Psychopharmacology 206, 653–664 (2009). https://doi.org/10.1007/s00213-008-1339-9

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  • DOI: https://doi.org/10.1007/s00213-008-1339-9

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