DIFFERENCES IN THE LIABILITY TO SELF-ADMINISTER INTRAVENOUS COCAINE BETWEEN C57BL 6XSJL AND BALB/CBYJ MICE/

Application of animal models of psychostimulant abuse for experimentat ion in mice is becoming increasingly important for studying the contri bution of genetic differences, as well as the roles of selected (targe ted) genes, in specific behaviors. The purpose of this study was to in vestigate strain. differences in cocaine self-administration behavior between C57BL/6 x SJL hybrid mice and BALB/cByJ mice. These two strain s were chosen because BALB/cByJ mice have a well-developed behavioral pharmacological profile, and hybrid strains on a C57BL/6 background ar e commonly used for generating transgenic expressing and knockout muta nt mice. C57BL/6 x SJL mice: dose-dependently acquired cocaine self-ad ministration (1.0 mg/kg/injection but not 0.25 mg/kg/injection) by res ponding selectively in the active nose-poke hole and maintaining stabl e levels of daily drug intake; they also exhibited a characteristic in verted-U-shaped cocaine dose-effect function. BALB/cByJ mice failed to acquire cocaine self-administration at either dose under the same tes t conditions. The strain differences observed in self-administration d id not seem to be attributed to other behavioral differences because t he two strains exhibited similar amounts of spontaneous nose-poking in the absence of reinforcers and BALB/cByJ mice responded more than C57 BL/6 x SJL mice in a food reinforced nose-poke operant task. Important ly, the dose-effect function for the motor stimulating effects of coca ine (3.8-30 mg/kg intraperitoneally) suggests enhanced sensitivity but reduced efficacy of cocaine in stimulating motor activity in BALB/cBy J mice relative to the C57BL/6 x SJL hybrid mice. These results indica te that the decreased liability of BALB/cByJ mice to acquire cocaine s elf-administration is not the result of differences in spontaneous act ivity or performance, but may reflect different sensitivities to the r einforcing, or rate-disrupting, properties of cocaine. The data suppor t an influence of generic background in the liability to self-administ er cocaine. Thus, a hypothesis is proposed that the decreased liabilit y of BALB/cByJ mice to acquire cocaine self-administration is related to differences in brain monoamine systems linked to the high ''emotion ality'' profile of BALB/c mice in novel or fearful situations, includi ng perhaps cocaine administration. (C) 1997 Elsevier Science Inc.