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Pharmacological manipulations of interval timing using the peak procedure in male C3H mice

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Abstract

Rationale

Timing deficits are characteristic of developmental and neurodegenerative disorders that are accompanied by cognitive impairment. A prominent theory of this interval timing posits an internal clock whose pace is modulated by the neurotransmitter dopamine.

Objectives

We tested two hypotheses about the pharmacology of interval timing in mice: (1) that general cognitive enhancers should increase, and cognitive disruptors should decrease temporal precision and (2) that acutely elevated dopamine should speed this internal clock and produce overestimation of elapsing time.

Materials and methods

C3H mice were tested in the peak procedure, a timing task, following acute administration of two putative cognitive enhancers (atomoxetine and physostigmine), two cognitive disruptors (scopolamine and chlordiazepoxide [CDP]), or two dopamine agonists (d-amphetamine and methamphetamine).

Results

The first hypothesis received strong support: temporal precision worsened with both cognitive disruptors, but improved with both cognitive enhancers. The two dopamine agonists also produced underestimation of elapsing time—congruent with the slowing of an internal clock and inconsistent with a dopamine-driven clock.

Conclusion

Our results suggest that interval timing has potential as an assay for generalized cognitive performance and that the dopamine-clock hypothesis needs further refinement.

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Authors and Affiliations

  1. PsychoGenics, Inc., 765 Old Saw Mill River Road, Tarrytown, NY, 10591, USA

    Fuat Balci, Brian D. Allen, Krystal M. Frank, Bryan J. Kapustinski, Thomas E. Fedolak & Daniela Brunner

  2. Department of Computing Science, University of Alberta, Edmonton, AB, Canada

    Elliot A. Ludvig

  3. Department of Psychology, Rutgers University, New Brunswick, NJ, USA

    Jacqueline M. Gibson

  4. Department of Psychiatry, Columbia University, New York, NY, USA

    Daniela Brunner

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  1. Fuat Balci
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  2. Elliot A. Ludvig
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  3. Jacqueline M. Gibson
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Correspondence to Fuat Balci.

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Balci, F., Ludvig, E.A., Gibson, J.M. et al. Pharmacological manipulations of interval timing using the peak procedure in male C3H mice. Psychopharmacology 201, 67–80 (2008). https://doi.org/10.1007/s00213-008-1248-y

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  • DOI: https://doi.org/10.1007/s00213-008-1248-y

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