Ketamine "unlocks" the reduced clock-speed effects of cocaine following extended training: evidence for dopamine--glutamate interactions in timing and time perception

Neurobiol Learn Mem. 2007 Sep;88(2):149-59. doi: 10.1016/j.nlm.2007.04.005. Epub 2007 May 21.

Abstract

The present study examined the clock-speed modulating effects of acute cocaine administration in groups of male rats that received different amounts of baseline training on a 36-s peak-interval procedure prior to initial drug injection. After injection of cocaine (10, 15, or 20mg/kg, ip), rats that had received a minimal amount of training (e.g., <or=30 sessions) prior to drug administration displayed a horizontal leftward shift in their timing functions indicating that the speed of the internal clock was increased. In contrast, rats that had received an extended amount of training (e.g., >or=180 sessions) prior to cocaine (15 mg/kg, ip) administration did not produce this "classic" curve-shift effect, but instead displayed a general disruption of temporal control following drug administration. Importantly, when co-administered with a behaviorally ineffective dose of ketamine (10mg/kg, ip) the ability of cocaine to modulate clock speed in rats receiving extended training was restored. A glutamate "lock/unlock" hypothesis is used to explain the observed dopamine-glutamate interactions as a function of timing behaviors becoming learned habits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks / drug effects*
  • Cocaine / antagonists & inhibitors*
  • Corpus Striatum / drug effects
  • Dopamine / metabolism*
  • Dopamine Uptake Inhibitors / antagonists & inhibitors*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Glutamic Acid / metabolism*
  • Habituation, Psychophysiologic / drug effects
  • Ketamine / pharmacology*
  • Learning / drug effects*
  • Male
  • Nerve Net / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Time Perception / drug effects*

Substances

  • Dopamine Uptake Inhibitors
  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Ketamine
  • Cocaine
  • Dopamine