A method for single-session cocaine self-administration in the mouse
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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.
KeywordsCocaine Self-administration Mouse
- Brabant C, Quertemont E, Tirelli E (2005) Evidence that the relations between novelty-induced activity, locomotor stimulation and place preference induced by cocaine qualitatively depend upon the dose: a multiple regression analysis in inbred C57BL/6J mice. Behav Brain Res 158:201–210PubMedCrossRefGoogle Scholar
- Mathon DS, Lesscher HM, Gerrits MA, Kamal A, Pintar JE, Schuller AG, Spruijt BM, Burbach JP, Smidt MP, van Ree JM, Ramakers GM (2005) Increased gabaergic input to ventral tegmental area dopaminergic neurons associated with decreased cocaine reinforcement in mu-opioid receptor knockout mice. Neuroscience 130:359–367PubMedCrossRefGoogle Scholar
- SAMHSA (2005) Results from the 2004 National Survey on Drug Use and Health: National FindingsGoogle Scholar
- Schramm-Sapyta NL, Olsen CM, Winder DG (2005) Cocaine self-administration reduces excitatory responses in the mouse nucleus accumbens shell. Neuropsychopharmacology (Epub ahead of print)Google Scholar