Ketamine "unlocks" the reduced clock-speed effects of cocaine following extended training: evidence for dopamine--glutamate interactions in timing and time perception.
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.
Cheng
Ruey-Kuang
RK
Department of Psychology and Neuroscience, Duke University, 572 Research Drive, Genome Sciences Research Building II, Box 91050, Durham, NC 27708, USA.
Ali
Yusuf M
YM
Meck
Warren H
WH
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D003042:Cocaine / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects*; D008297:Male; D009415:Nerve Net / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013998:Time Perception / Q000187:drug effects*
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D007649:Ketamine; D003042:Cocaine; D004298:Dopamine