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Psychopharmacology (Berl). 2013 Feb;225(4):935-44. doi: 10.1007/s00213-012-2877-8. Epub 2012 Sep 20.

Examination of behavioral strategies regulating cocaine intake in rats.

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Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Medical Center BLVD, Winston-Salem, NC 27157, USA.



It has long been observed that rats self-administer psychostimulants in a highly regular pattern. The inverse relationship between dose and rate of drug intake has been interpreted as a titration phenomenon wherein brain-cocaine levels are maintained within a range. Most studies examining this phenomenon have used fixed, unit doses in which case the only titration strategy available to the animal is to adjust inter-infusion intervals.


In this study, we examined whether selection of dose size could also be a factor in regulation of intake. We used a schedule of reinforcement, under which the dose can vary through a wide range and is determined by the behavior of the animal.


Rats self-administered cocaine using a behaviorally dependent dosing schedule of reinforcement, under which the size of each dose was determined by the length of time the lever was held down. The concentration of cocaine was changed across sessions.


Total pump-time self-administered decreased by 56 % following each doubling of the concentration, which led to an average 11 % increase in total intake. Similarly, estimated brain levels of cocaine increased by 12 % for each doubling of concentration. These adjustments were the result of manipulation of both the size and spacing of infusions.


In agreement with previous studies, the regular pattern of intake appears to be the result of a titration mechanism in which animals maintain brain levels of cocaine above some threshold. Compensatory regulation appeared to involve both the selection of dose size and inter-infusion intervals.

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