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

Psychopharmacology (Berl). 2008 Nov;201(1):67-80. doi: 10.1007/s00213-008-1248-y. Epub 2008 Jul 23.


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.

MeSH terms

  • Animals
  • Atomoxetine Hydrochloride
  • Behavior, Animal
  • Chlordiazepoxide / pharmacology
  • Cognition / drug effects
  • Cognition / physiology
  • Cognition Disorders / physiopathology
  • Cognition Disorders / psychology
  • Conditioning, Operant / drug effects
  • Dextroamphetamine / pharmacology
  • Dopamine Agonists / pharmacology
  • Dose-Response Relationship, Drug
  • Injections, Intraperitoneal
  • Male
  • Methamphetamine / pharmacology
  • Mice
  • Mice, Inbred C3H / physiology*
  • Mice, Inbred C3H / psychology*
  • Nootropic Agents / pharmacology
  • Physostigmine / pharmacology
  • Propylamines / pharmacology
  • Psychophysiology / methods
  • Reaction Time / drug effects*
  • Reaction Time / physiology
  • Scopolamine / pharmacology
  • Sodium Chloride / administration & dosage
  • Statistics as Topic / methods
  • Time Factors
  • Time Perception / physiology


  • Dopamine Agonists
  • Nootropic Agents
  • Propylamines
  • Methamphetamine
  • Sodium Chloride
  • Atomoxetine Hydrochloride
  • Chlordiazepoxide
  • Physostigmine
  • Scopolamine
  • Dextroamphetamine