Brain-Cocaine Concentrations Determine the Dose Self-Administered by Rats on a Novel Behaviorally Dependent Dosing Schedule

A novel behaviorally dependent dosing (BDD) schedule was used to examine the relationship between doses of cocaine self-administered by rats and brain drug levels within a session. The BDD schedule used a hold-down response to activate a syringe pump. The length of time the lever was held down deter...

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Bibliographic Details
Published in:Neuropsychopharmacology (New York, N.Y.) N.Y.), 2011-12, Vol.36 (13), p.2741-2749
Main Authors: ZIMMER, Benjamin A, DOBRIN, Carson V, ROBERTS, David Cs
Format: Article
Language:English
Subjects:
Animals
Behavior, Animal - drug effects
Behavior, Animal - physiology
Biological and medical sciences
Brain Chemistry - drug effects
Brain Chemistry - physiology
Cocaine
Cocaine - administration & dosage
Cocaine - metabolism
Cocaine - pharmacokinetics
Cocaine-Related Disorders - metabolism
Disease Models, Animal
Dopamine Uptake Inhibitors - metabolism
Dopamine Uptake Inhibitors - pharmacokinetics
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug dosages
Experiments
Health sciences
Male
Medical sciences
Neuropharmacology
Original
Pharmacology. Drug treatments
Physiology
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Rats, Sprague-Dawley
Self Administration - methods
Surgery
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Summary:A novel behaviorally dependent dosing (BDD) schedule was used to examine the relationship between doses of cocaine self-administered by rats and brain drug levels within a session. The BDD schedule used a hold-down response to activate a syringe pump. The length of time the lever was held down determined the duration that the syringe pump was activated. In the first experiment, rats self-administered cocaine for daily 3 h sessions and brain levels of cocaine were modeled using well-established parameters. Although analysis revealed that rats self-administered doses within a predicted range, one extremely large dose was consistently observed at the beginning of each session when brain levels of cocaine were low. In the second experiment, we introduced a range of timeout periods (10-25 min) in order to produce variability in brain-cocaine concentrations. Animals self-administered larger doses immediately following each timeout period and the dose size was inversely correlated with the length of the timeout. These results show that the dose of cocaine that rats self-administer within a session is inversely related to the amount of drug on board.
ISSN:0893-133X
1740-634X
DOI:10.1038/npp.2011.165