Reinforcing and Neurochemical Effects of Cocaine: Differences Among C57, DBA, and 129 Mice

Abstract

C57BL/6J, DBA/2J, and 129/OlaHsd mice were compared as to their propensity to self-administer cocaine, the ability of cocaine injection to prevent extinction of nose poking in the absence of cocaine infusion, and cocaine's effect on NGFI-A and secretogranin II mRNA. Baseline nose-poke activity tended to be highest in C57 and lowest in DBA mice. C57 and DBA mice self-administered cocaine, as indicated by more frequent nose pokes in mice allowed to infuse cocaine through nose pokes than in mice passively receiving the same amount of cocaine. DBA mice had the larger ratio between active and yoked-control animals, but the response rate in DBA mice was four times lower, and cocaine intake 10 times lower than in C57 mice. The 129 mice showed little response to cocaine. C57 and DBA mice that had been self-administering cocaine showed an extinction of responding when infusions were stopped, preventable by IP cocaine (5 mg kg − 1). A single cocaine injection (2 mg kg − 1) increased NGFI-A mRNA and decreased secretogranin II mRNA in the caudate putamen in C57 mice. These effects were more widespread in DBA and absent in the 129 mice. The marked differences among mouse strains described here will be important to consider when transgenic mice are to be used in cocaine-related studies.