Ristuccia Robert C, Hernandez Michael, Wilmouth Carrie E, Spear Linda P
Department of Psychology, Center for Developmental Psychobiology, Binghamton University, Binghamton, New York 13902-6000, USA.
Alcohol Clin Exp Res. 2007 Apr;31(4):575-81. doi: 10.1111/j.1530-0277.2007.00341.x.
Previous work examining ethanol's autonomic effects has found contrasting patterns of age-related differences in ethanol-induced hypothermia between adolescent and adult rats. Most studies have found adolescents to be less sensitive than adults to this effect, although other work has indicated that adolescents may be more sensitive than adults under certain testing conditions. To test the hypothesis that adolescents show more ethanol hypothermia than adults when the amount of disruption induced by the test procedures is low, but less hypothermia when the experimental perturbation is greater, the present study examined the consequences of manipulating the amount of perturbation at the time of testing on ethanol-induced hypothermia in adolescent and adult rats.
The amount of test disruption was manipulated by administering ethanol through a chronically indwelling gastric cannula (low perturbation) versus via intragastric intubation (higher perturbation) in Experiment 1 or by either familiarizing animals to the handling and injection procedure for several days pretest or leaving them unmanipulated before testing in Experiment 2.
The results showed that the handling manipulation, but not the use of gastric cannulae, altered the expression of ethanol-induced hypothermia differentially across age. When using a familiarization protocol sufficient to reduce the corticosterone response to the handling and injection procedure associated with testing, adolescents showed greater hypothermia than adults. In contrast, the opposite pattern of age differences in hypothermia was evident in animals that were not manipulated before the test day. Surprisingly, however, this difference across testing circumstances was driven by a marked reduction in hypothermia among adults who had been handled before testing, with handling having relatively little impact on ethanol hypothermia among adolescents.
Observed differences between adolescents and adults in the autonomic consequences of ethanol were dramatically influenced by whether animals were familiarized with the handling/injection process before testing. Under these circumstances, adolescents were less susceptible than adults to the impact of experimental perturbation on ethanol-induced hypothermia. These findings suggest that seemingly innocuous aspects of experimental design can influence conclusions reached on ontogenetic differences in sensitivity to ethanol, at least when indexed by ethanol-induced hypothermia.
先前有关乙醇自主神经效应的研究发现,青春期大鼠和成年大鼠在乙醇诱导的体温过低方面存在与年龄相关的差异,且模式相互矛盾。大多数研究发现,青春期大鼠对这种效应的敏感性低于成年大鼠,不过其他研究表明,在某些测试条件下,青春期大鼠可能比成年大鼠更敏感。为了验证这一假设,即当测试程序引起的干扰量较低时,青春期大鼠比成年大鼠表现出更多的乙醇诱导体温过低,但当实验干扰较大时,体温过低现象则较少,本研究考察了在测试时操纵干扰量对青春期和成年大鼠乙醇诱导体温过低的影响。
在实验1中,通过长期留置胃插管给予乙醇(低干扰)与通过胃内插管给予乙醇(高干扰)来操纵测试干扰量,或者在实验2中,在测试前几天让动物熟悉处理和注射程序,或者在测试前不进行任何处理。
结果表明,处理操作而非胃插管的使用,在不同年龄组中对乙醇诱导体温过低的表现有不同影响。当采用足以降低与测试相关的处理和注射程序引起的皮质酮反应的熟悉方案时,青春期大鼠比成年大鼠表现出更高的体温过低。相反,在测试当天未进行处理的动物中,体温过低的年龄差异模式则相反。然而,令人惊讶的是,这种测试条件下的差异是由测试前接受处理的成年大鼠体温过低显著降低所驱动的,而处理对青春期大鼠的乙醇诱导体温过低影响相对较小。
青春期大鼠和成年大鼠在乙醇自主神经效应方面的差异,受到动物在测试前是否熟悉处理/注射过程的显著影响。在这种情况下,青春期大鼠比成年大鼠更不易受到实验干扰对乙醇诱导体温过低的影响。这些发现表明,实验设计中看似无害的方面可能会影响关于乙醇敏感性个体发育差异得出的结论,至少在以乙醇诱导体温过低为指标时是如此。