Laboratoire de Biologie du Comportement, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
Alcohol Alcohol. 2009 Nov-Dec;44(6):535-46. doi: 10.1093/alcalc/agp047. Epub 2009 Sep 8.
The possible interaction between nicotine and 'binge drinking' in eliciting changes in behavioural patterns of 'binge drinking' rats as well as nucleus accumbens (NAc) glutamate levels has been investigated in these present studies.
Adult or adolescent male and female rats received ethanol, 2 g/kg or 3 g/kg, by gavage in a 'binge drinking' regimen (3 times/day over a 6 h period, for 2 days followed by 5 days of abstinence) combined with or without nicotine, 0.3 g/kg, for either a 5-week (adult) or a 4-week (adolescent) period. Motor activity was then assessed for a period of 60 min after three further doses of ethanol or water. In addition, the NAc glutamate level was assayed in each group for 1 h after the first gavage regimen with ethanol, 2 g/kg or 3 g/kg, or water.
Adult female rats showed greater sensitivity to each ethanol dose (2 g/kg and 3 g/kg) than the adult male rats, their motor activity decreasing during the first and third 'binge'. In contrast, in male adult rats, the sedative effects of ethanol were reduced, particularly after the third binge when no significant changes in the locomotor activity were apparent between the ethanol-administered male rats and controls. Adolescent rats did differ in their response to ethanol in comparison with adult rats. It was noteworthy that in young female adolescent rats, given 2 g/kg ethanol, motor activity was enhanced, thereby indicating that adolescent female rats are less sensitive to the sedative effects of ethanol at specific doses. In addition, male and female adolescent rats showed little change in locomotor activity in comparison with controls during the third 'binge administration' possibly indicating that tolerance to such alcohol doses was occurring. Nicotine administration did prevent the decrease in locomotor activity after ethanol administration during the first binge regimen in both male and female adolescents as well as adult female rats. However, after the third binge, such alcohol-induced changes in motor activity were not so well defined in the female adult rats that now showed significant decreases in motor activity. In contrast, adolescent male and female rats still showed similar motor activity to that of the controls. No clear association between the NAc glutamate extracellular content and locomotor activity was discernible in either adult or adolescent rats in these present studies. However, chronic nicotine administration markedly reduced the elevated basal glutamate content in the 'binge drinking female' adult rats.
These studies have shown clear and distinct differences, with respect to both sensitivity and tolerance, in adult and adolescent male and female rats, which could be modified by supplementation with nicotine.
本研究旨在探讨尼古丁与“狂饮”之间的相互作用，以观察其对“狂饮”大鼠行为模式及伏隔核（NAc）谷氨酸水平的影响。
成年或青春期雄性和雌性大鼠接受灌胃乙醇（2 g/kg 或 3 g/kg），采用“狂饮”方案（6 h 内 3 次，连续 2 天，随后 5 天禁欲），同时给予或不给予尼古丁（0.3 g/kg），持续 5 周（成年）或 4 周（青春期）。然后在再给予 3 次乙醇或水后，评估 60 分钟的运动活动。此外，在第一次给予 2 g/kg 或 3 g/kg 乙醇或水后 1 小时，检测每组 NAc 谷氨酸水平。
成年雌性大鼠对每个乙醇剂量（2 g/kg 和 3 g/kg）的敏感性均高于成年雄性大鼠，它们的运动活动在第一次和第三次“狂饮”期间减少。相反，在雄性成年大鼠中，乙醇的镇静作用减弱，特别是在第三次狂饮后，接受乙醇治疗的雄性大鼠与对照组之间的运动活动没有明显变化。与成年大鼠相比，青春期大鼠对乙醇的反应有所不同。值得注意的是，给予 2 g/kg 乙醇的年轻雌性青春期大鼠的运动活动增强，这表明特定剂量的青春期雌性大鼠对乙醇的镇静作用不敏感。此外，雄性和雌性青春期大鼠在第三次“狂饮”期间与对照组相比，运动活动几乎没有变化，这可能表明它们对这些酒精剂量产生了耐受性。尼古丁给药可防止雄性和雌性青春期大鼠以及成年雌性大鼠在第一次狂饮期间乙醇给药后运动活动的减少。然而，在第三次狂饮后，雌性成年大鼠的这种酒精诱导的运动活动变化不再明显，现在显示出明显的运动活动减少。相比之下，青春期雄性和雌性大鼠的运动活动仍与对照组相似。在本研究中，无论是成年大鼠还是青春期大鼠，都没有发现 NAc 谷氨酸细胞外含量与运动活动之间有明显的关联。然而，慢性尼古丁给药显著降低了“狂饮女性”成年大鼠基础谷氨酸含量的升高。
这些研究表明，成年和青春期雄性和雌性大鼠在敏感性和耐受性方面存在明显差异，这种差异可通过尼古丁补充来改变。
