Lessov C N, Palmer A A, Quick E A, Phillips T J
Washington University School of Medicine, Department of Psychiatry, 40 N Kingshighway, Suite 1, St. Louis, MO 63108, USA.
Psychopharmacology (Berl). 2001 Apr;155(1):91-9. doi: 10.1007/s002130100699.
Drug-induced sensitization has been associated with enhanced drug self-administration and may contribute to drug addiction.
We investigated the possible association between sensitization to the locomotor stimulant effects of ethanol (EtOH) and voluntary EtOH consumption.
Mice of the EtOH-avoiding DBA/2J (D2) and EtOH-preferring C57BL/6J (B6) inbred strains were offered the choice of an EtOH solution versus tap water (EtOH-experienced) or just water (Na), and voluntary consumption was measured. Mice from each condition then received repeated EtOH or saline injections, and locomotor responses were measured. Subsequently, all mice were offered the choice of EtOH versus water, and voluntary consumption was again measured. A subsequent study examined relative susceptibility of D2 and B6 mice to EtOH-induced locomotor sensitization.
Voluntary EtOH consumption induced locomotor sensitization to an EtOH challenge in B6 mice. D2 mice consumed little EtOH, but developed sensitization with repeated EtOH treatments as expected. EtOH consumption was not altered in EtOH-sensitized D2 mice. Unexpectedly, B6 mice developed significant sensitization, and following sensitization, the EtOH-experienced EtOH-sensitized group consumed more EtOH than their EtOH-experienced salinetreated (non-sensitized) counterparts. In an independent study, B6 mice required between three and five EtOH injections to express sensitization, whereas for D2 mice, between one and three EtOH exposures were sufficient.
Development of sensitization to the locomotor stimulant effects of EtOH may be associated with increased EtOH consumption in mice with high initial avidity for EtOH. In the same mice, voluntary EtOH consumption can also produce behavioral sensitization to the effects of EtOH.
药物诱导的致敏作用与增强的药物自我给药有关,可能导致药物成瘾。
我们研究了对乙醇(EtOH)运动刺激作用的致敏与自愿乙醇消费之间的可能关联。
为乙醇回避型近交系DBA/2J(D2)和乙醇偏好型近交系C57BL/6J(B6)小鼠提供乙醇溶液与自来水(有乙醇经验)或仅水(无乙醇经验)的选择,并测量自愿消费量。然后,对每种条件下的小鼠进行重复的乙醇或盐水注射,并测量运动反应。随后,为所有小鼠提供乙醇与水的选择,并再次测量自愿消费量。随后的一项研究检查了D2和B6小鼠对乙醇诱导的运动致敏的相对易感性。
自愿乙醇消费在B6小鼠中诱导了对乙醇激发的运动致敏。D2小鼠很少饮用乙醇,但如预期的那样,随着乙醇的重复处理出现了致敏。乙醇致敏的D2小鼠的乙醇消费量没有改变。出乎意料的是,B6小鼠出现了显著的致敏,并且在致敏后,有乙醇经验的乙醇致敏组比有乙醇经验的盐水处理(未致敏)组消耗更多的乙醇。在一项独立研究中,B6小鼠需要三到五次乙醇注射才能表现出致敏,而对于D2小鼠,一到三次乙醇暴露就足够了。
对乙醇运动刺激作用的致敏发展可能与对乙醇初始亲和力高的小鼠中乙醇消费量增加有关。在同一小鼠中,自愿乙醇消费也可产生对乙醇作用的行为致敏。