Nizhnikov Michael E, Varlinskaya Elena I, Spear Norman E
Department of Psychology, Center for Developmental Psychobiology, Binghamton University-SUNY, Binghamton, New York 13902, USA.
Alcohol Clin Exp Res. 2006 Dec;30(12):2089-96. doi: 10.1111/j.1530-0277.2006.00253.x.
Newborn rat pups readily ingest ethanol of low to moderate concentrations and are sensitive to its reinforcing effects. Given that early ethanol exposure can promote its future abuse, it is vital to discover the mechanisms behind reinforcing effects of ethanol at this stage of life.
Cesarean-delivered 3- to 4-hour-old rat pups were exposed to lemon odor (unconditioned stimulus) either paired or explicitly unpaired with central injections of saline or ethanol (25, 50, 100, 200, or 400 mg%) in a volume of 1 muL. One hour following conditioning subjects were tested on a surrogate nipple providing water in the presence of lemon odor. Reinforcement from ethanol's central effects was indexed by significantly greater attachment time on a lemon-scented nipple in paired subjects than in unpaired or saline controls.
Rats centrally injected with 25 to 200 mg% ethanol in the presence of lemon odor spent significantly more time attached to a lemon-scented surrogate nipple providing water than did their saline-injected or unpaired counterparts. Those injected with 400 mg% ethanol did not differ from their corresponding controls. No detectable brain alcohol content was found in the assay of whole brain for ethanol levels.
These results indicate that 3- to 4-hour-old rat pups find central injections of 25 to 200 mg% ethanol reinforcing. This procedure virtually eliminates ethanol's chemosensory or caloric attributes as the source of ethanol reinforcement. The present classical olfactory conditioning paradigm can be used to further study mechanisms of this apparently pharmacological reinforcement by ethanol in newborn rat pups.
新生大鼠幼崽容易摄入低至中等浓度的乙醇,并且对其强化作用敏感。鉴于早期乙醇暴露会促进其未来的滥用,在生命的这个阶段发现乙醇强化作用背后的机制至关重要。
通过剖宫产取出3至4小时大的大鼠幼崽,将柠檬气味(非条件刺激)与1微升体积的生理盐水或乙醇(25、50、100、200或400毫克%)的中枢注射进行配对或明确不配对。在条件反射后1小时,在柠檬气味存在的情况下,对受试对象在提供水的替代乳头上进行测试。乙醇中枢作用的强化通过配对受试对象在柠檬味乳头上的附着时间显著长于未配对或生理盐水对照组来衡量。
在柠檬气味存在的情况下,中枢注射25至200毫克%乙醇的大鼠在附着于提供水的柠檬味替代乳头上的时间明显长于注射生理盐水或未配对的大鼠。注射400毫克%乙醇的大鼠与相应对照组没有差异。在全脑乙醇水平测定中未发现可检测到的脑乙醇含量。
这些结果表明,3至4小时大的大鼠幼崽发现中枢注射25至200毫克%乙醇具有强化作用。该程序实际上消除了乙醇的化学感觉或热量属性作为乙醇强化的来源。目前的经典嗅觉条件反射范式可用于进一步研究新生大鼠幼崽中乙醇这种明显的药理学强化作用的机制。