Cao W, Burkholder T, Wilkins L, Collins A C
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Pharmacol Biochem Behav. 1993 Aug;45(4):803-9. doi: 10.1016/0091-3057(93)90124-c.
Human alcoholics are almost invariably heavy users of tobacco, perhaps because both ethanol and nicotine may have anxiolytic activity. However, studies in humans have not uniformly detected anxiolytic effects because significant individual differences in anxiolytic actions of these agents seem to exist. One factor that seems to contribute to these individual differences is tolerance to ethanol. Individuals who are more sensitive to depressant actions of alcohol seem to show anxiolytic actions more readily. Consequently, we examined the relative sensitivities of the ethanol-sensitive (to the anesthetic actions of ethanol) long-sleep (LS) and ethanol-resistant short-sleep (SS) mouse lines to diazepam, ethanol, nicotine, and ethanol-nicotine combinations in the mirrored chamber test. This test measures approach-conflict behavior. Ethanol and nicotine evoked changes in mirrored chamber activities that resembled those elicited by diazepam. These effects were seen at doses that did not markedly affect locomotor activity, thereby suggesting that these changes in behavior represent anxiolytic actions. The LS-SS mice did not differ in sensitivity to diazepam, but the SS were more uniformly responsive to the other drugs. Only the SS showed clear evidence for interactions between ethanol and nicotine. If the changes in mirrored chamber behavior elicited by ethanol, nicotine, and combinations of the two drugs occur because of anxiety reduction, it seems that the SS mouse line is more responsive to anxiolytic actions of these drugs.
人类酗酒者几乎无一例外都是重度吸烟者,这可能是因为乙醇和尼古丁都可能具有抗焦虑活性。然而,对人类的研究并未一致检测到抗焦虑作用,因为这些药物的抗焦虑作用似乎存在显著的个体差异。一个似乎导致这些个体差异的因素是对乙醇的耐受性。对酒精抑制作用更敏感的个体似乎更容易表现出抗焦虑作用。因此,我们在镜像箱试验中检测了对乙醇敏感(对乙醇麻醉作用敏感)的长睡眠(LS)和乙醇耐受的短睡眠(SS)小鼠品系对安定、乙醇、尼古丁以及乙醇 - 尼古丁组合的相对敏感性。该试验测量接近冲突行为。乙醇和尼古丁引起的镜像箱活动变化类似于安定引起的变化。这些作用在对运动活动没有明显影响的剂量下即可观察到,从而表明这些行为变化代表抗焦虑作用。LS - SS小鼠对安定的敏感性没有差异,但SS对其他药物的反应更一致。只有SS显示出乙醇和尼古丁之间相互作用的明确证据。如果乙醇、尼古丁以及这两种药物组合引起的镜像箱行为变化是由于焦虑减轻所致,那么似乎SS小鼠品系对这些药物的抗焦虑作用更敏感。