A method for single-session cocaine self-administration in the mouse
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- Olsen, C.M. & Winder, D.G. Psychopharmacology (2006) 187: 13. doi:10.1007/s00213-006-0388-1
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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.
We set out to develop a methodology in mice for obtaining high levels of cocaine self-administration during the first exposure to the drug.
Materials and 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.
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.
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.