Alcohol and Drug Abuse Research Center, Harvard Medical School and McLean Hospital, Mail Stop 214,115 Mill Street, Belmont, MA 02478, USA.
Exp Clin Psychopharmacol. 2011 Oct;19(5):321-41. doi: 10.1037/a0024798.
Relative to intravenous drug self-administration, locomotor activity is easier to measure with high throughput, particularly in mice. Therefore its potential to predict differences in self-administration between genotypes (e.g., targeted mutations, recombinant inbred strains) is appealing, but such predictive value is unverified. The main goal of this study was to evaluate the utility of the locomotor assay for accurately predicting differences in cocaine self-administration. A second goal was to evaluate any correlation between activity in a novel environment, and cocaine-induced hyperactivity, between strains. We evaluated locomotor activity in male and female Sprague-Dawley rats and 15 mouse strains (129S1/SvImJ, 129S6/SvEvTac, 129X1/SvJ, A/J, BALB/cByJ, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, SJL/J, SPRET/EiJ, and outbred Swiss Webster and CD-1/ICR), as well as cocaine self-administration in BALB substrains. All but BALB/cJ mice showed locomotor habituation and significant cocaine-induced hyperactivity. BALB/cJ mice also failed to self-administer cocaine. BALB/cByJ mice showed modest locomotor habituation, cocaine-induced locomotion, and cocaine self-administration. As previously reported, female rats showed greater cocaine-induced locomotion than males, but this was only observed in one of 15 mouse strains (FVB/NJ), and the reverse was observed in two strains (129X1/SvJ, BALB/cByJ). The intriguing phenotype of the BALB/cJ strain may indicate some correlation between all-or-none locomotion in a novel environment, and stimulant and reinforcing effects of cocaine. However, neither novelty- nor cocaine-induced activity offered a clear prediction of relative reinforcing effects among strains. Additionally, these results should aid in selecting mouse strains for future studies in which relative locomotor responsiveness to psychostimulants is a necessary consideration.
与静脉内药物自我给药相比，运动活动更容易进行高通量测量，尤其是在小鼠中。因此，它有可能预测基因型之间自我给药的差异（例如，靶向突变，重组近交系），但这种预测价值尚未得到验证。本研究的主要目的是评估运动测定法在准确预测可卡因自我给药差异方面的效用。第二个目标是评估在不同品系之间，新环境中的活动与可卡因引起的过度活动之间的任何相关性。我们评估了雄性和雌性 Sprague-Dawley 大鼠以及 15 种小鼠品系（129S1/SvImJ、129S6/SvEvTac、129X1/SvJ、A/J、BALB/cByJ、BALB/cJ、C3H/HeJ、C57BL/6J、CAST/EiJ、DBA/2J、FVB/NJ、SJL/J、SPRET/EiJ 和杂交瑞士 Webster 以及 CD-1/ICR）以及 BALB 亚系中的可卡因自我给药。除了 BALB/cJ 小鼠外，所有小鼠均表现出运动习惯化和明显的可卡因诱导的过度活跃。BALB/cJ 小鼠也未能自我给予可卡因。BALB/cByJ 小鼠表现出适度的运动习惯化，可卡因诱导的运动和可卡因自我给药。如前所述，雌性大鼠比雄性大鼠表现出更大的可卡因诱导的运动，但这种现象仅在 15 种小鼠品系之一（FVB/NJ）中观察到，而在两种品系（129X1/SvJ，BALB/cByJ）中则相反。BALB/cJ 品系的引人入胜的表型可能表明，在新环境中，运动的全有或全无与可卡因的刺激和强化作用之间存在某些相关性。然而，无论是新奇感还是可卡因诱导的活动，都无法清晰地预测不同品系之间的相对强化作用。此外，这些结果有助于选择用于未来研究的小鼠品系，其中对精神兴奋剂的相对运动反应性是必要的考虑因素。
