A method for single-session cocaine self-administration in the mouse.
BACKGROUND
Drug self-administration is a powerful method to measure the reinforcing effects of a drug, as well as to investigate behavioral, biochemical, and physiological effects of a drug specific to contingent delivery. With the spectrum of genetically modified mice available, there is a need for well-designed drug self-administration studies tailored for rapid completion of studies in mice.


OBJECTIVE
We set out to develop a methodology in mice for obtaining high levels of cocaine self-administration during the first exposure to the drug.


METHODS
C57Bl/6J mice were trained to lever press for liquid reinforcer on a fixed ratio 1, then a progressive ratio (PR) schedule of reinforcement before intravenous self-administration of cocaine on a PR schedule.


RESULTS
Within a single 16-h session, each mouse self-administered either saline or 0.1, 0.3, 0.6, or 1.2 mg kg(-1) infusion(-1) of cocaine during four distinct 4-h subsessions. Mice showed a strong preference for cocaine vs saline, as demonstrated by higher breakpoints and greater preference for the active lever. Likewise, there was a dose-dependent increase in breakpoints obtained and in drug intake. Finally, animals receiving noncontingent cocaine pressed significantly less than mice self-administering the same dose of cocaine, indicating that a significant amount of active lever pressing is driven by drug-seeking and not the psychomotor-activating effects of cocaine alone.


CONCLUSIONS
Mice will reach high breakpoints and cocaine intake during an initial exposure to cocaine. This method is well-suited to rapidly obtain progressive ratio cocaine self-administration in mice.
Olsen
Christopher M
CM
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232-0615, USA. chris.olsen@vanderbilt.edu
Winder
Danny G
DG
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012055:Reinforcement Schedule; D012646:Self Administration
D003042:Cocaine