Roma Peter G, Chen Scott A, Barr Christina S, Riley Anthony L
Psychopharmacology Laboratory, Department of Psychology, American University, 4400 Massachusetts Avenue, NW, Washington, DC, USA.
Behav Brain Res. 2007 Aug 22;182(1):51-6. doi: 10.1016/j.bbr.2007.05.012. Epub 2007 May 13.
In humans and laboratory animal models, vulnerability to alcohol abuse is influenced by endogenous factors such as genotype. Using the inbred Fischer and Lewis rat strains, we previously reported stronger conditioned taste aversions (CTA) in male Fischer rats that could not be predicted by genotypic differences in alcohol absorption [Roma PG, Flint WW, Higley JD, Riley AL. Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats. Psychopharmacology (Berl) 2006;189:187-99]. The present study made similar assessments in Fischer and Lewis females via four-trial CTA induced by 1 or 1.5 g/kg intraperitoneal (IP) ethanol (n=10-12/strain/dose) as well as measures of blood alcohol concentrations (BAC) at 15, 60 and 180 min post-injection with 1.5 g/kg IP ethanol or saline (n=7-8/strain/dose). Dose-dependent CTAs were produced, but the strains did not differ from each other in these measures; however, BACs in the Lewis females were significantly higher than Fischer at all three time points. As with males of the Fischer and Lewis genotypes, a dissociation between BACs and the aversive effects of alcohol was observed. These data are the first assessments of these particular phenotypes in Fischer and Lewis females, and when considered with the historical data, suggest a Genotype x Sex interaction in the centrally mediated sensitivity to alcohol's aversive effects.
在人类和实验动物模型中，酗酒易感性受基因型等内源性因素影响。利用近交系Fischer大鼠和Lewis大鼠品系，我们之前报道过雄性Fischer大鼠有更强的条件性味觉厌恶（CTA），而这无法通过酒精吸收的基因型差异来预测[Roma PG, Flint WW, Higley JD, Riley AL. Fischer大鼠和Lewis大鼠对酒精厌恶和奖赏作用的评估。《精神药理学》（柏林）2006年；189:187 - 99]。本研究通过腹腔注射（IP）1或1.5 g/kg乙醇诱导的四次试验CTA（每个品系/剂量组n = 10 - 12）以及在腹腔注射1.5 g/kg乙醇或生理盐水后15、60和180分钟时的血液酒精浓度（BAC）测量（每个品系/剂量组n = 7 - 8），对Fischer大鼠和Lewis大鼠雌性进行了类似评估。产生了剂量依赖性CTA，但在这些测量中品系间没有差异；然而，在所有三个时间点，Lewis雌性大鼠的BAC均显著高于Fischer大鼠。与Fischer和Lewis基因型的雄性大鼠一样，观察到BAC与酒精厌恶效应之间的分离。这些数据是对Fischer大鼠和Lewis大鼠雌性这些特定表型的首次评估，结合历史数据来看，表明在对酒精厌恶效应的中枢介导敏感性方面存在基因型×性别相互作用。
