Women acquire cocaine habits faster and are more motivated to obtain drug than men. In general, female rodents acquire intravenous cocaine self-administration (SA) faster and show greater locomotor responses to cocaine than males. Sex differences are attributed to differences in circulating estradiol. We used the four core genotype (FCG) mouse to ask whether sex chromosome complement influences vulnerability to cocaine's reinforcing and/or locomotor-activating effects. The FCG cross produces ovary-bearing mice with XX or XY genotypes (XXF, XYF) and testes-bearing mice with XX or XY genotypes (XXM, XYM). A greater percentage of gonadal females acquired cocaine SA via infusions into jugular catheters as compared with XYM mice, but XXM mice were not significantly different than any other group. Discrimination of the active versus inactive nose poke holes and cocaine intake were in general greater in gonadal females than in gonadal males. Progressive ratio tests for motivation revealed an interaction between sex chromosomes and gonads: XYM mice were more motivated to self-administer cocaine taking more infusions than mice in any other group. Locomotor responses to cocaine exposure revealed effects of sex chromosomes. After acute exposure, activity was greater in XX than in XY mice and the reverse was true for behavioral sensitization. Mice with XY genotypes displayed more activity than XX mice when given cocaine after a 10-day drug-free period. Our data demonstrate that sex chromosome complement alone and/or interacting with gonadal status can modify cocaine's reinforcing and locomotor-activating effects. These data should inform current studies of sex differences in drug use.

与男性相比，女性更快地养成可卡因习惯，并且更有动力获得毒品。一般来说，雌性啮齿动物比雄性更快地获得静脉内可卡因自我给药 (SA)，并对可卡因表现出更大的运动反应。性别差异归因于循环雌二醇的差异。我们使用四核心基因型 (FCG) 小鼠来询问性染色体补体是否会影响对可卡因增强和/或运动激活作用的脆弱性。FCG 杂交产生具有 XX 或 XY 基因型 (XXF, XYF) 的带卵巢小鼠和具有 XX 或 XY 基因型 (XXM, XYM) 的带睾丸小鼠。与 XYM 小鼠相比，更大比例的性腺雌性通过注入颈静脉导管获得可卡因 SA，但 XXM 小鼠与任何其他组没有显着差异。性腺女性对活跃和不活跃的鼻子戳孔和可卡因摄入量的区分通常比性腺男性要大。动机的渐进式比率测试揭示了性染色体和性腺之间的相互作用：XYM 小鼠比任何其他组的小鼠更愿意自我给药可卡因，并接受更多的输注。对可卡因暴露的运动反应揭示了性染色体的影响。急性暴露后，XX 小鼠的活性高于 XY 小鼠，而行为敏化则相反。在 10 天无毒期后给予可卡因时，具有 XY 基因型的小鼠比 XX 小鼠表现出更多的活动。我们的数据表明，单独的性染色体补充和/或与性腺状态相互作用可以改变可卡因的增强和运动激活作用。