Mazurski E J, Beninger R J
Department of Psychology, Queen's University, Kingston, Canada.
Pharmacol Biochem Behav. 1988 Feb;29(2):249-55. doi: 10.1016/0091-3057(88)90153-0.
The stimulants (+)-amphetamine and apomorphine are known to increase motility and induce stereotypy in rats. The present study examined the effects of an habituation period immediately prior to injection on these stimulant effects. Male Wistar rats received doses of either drug including 0, 0.01, 0.1, 0.25, 1.0, 2.0 and 4.0 mg/kg in a random order. Activity was assessed in 6 automated chambers where horizontal and vertical activity were tabulated hourly for 4 hours. Initially all rats had equal exposure to the chambers over 5 days. In the subsequent drug phase, habituated rats were placed in the chambers for the 1-hr period prior to each injection whereas non-habituated rats were in their home cages at the corresponding time. (+)-Amphetamine stimulated horizontal activity, although under either condition the effect was not seen until the second hour post-injection, but lasted until the fourth hour. Vertical activity was similarly enhanced, but with habituation there was a significant stimulant effect in the first hour as well. With apomorphine the habituation period resulted in an absence of a significant stimulant effect. Non-habituated rats showed a significant stimulant effect with the highest dose only on vertical activity in the first hour and a stimulant effect with horizontal activity in the second hour. It is suggested that the relative novelty of the environment affected the behavioral response to apomorphine but not to (+)-amphetamine. Furthermore, the activating effects accompanying drug administration should be taken into account as a factor affecting responses to drugs. Such environmental factors may be of particular importance when considering drugs with a short duration of action.
已知兴奋剂(+)-苯丙胺和阿扑吗啡可增加大鼠的运动能力并诱发刻板行为。本研究考察了注射前的适应期对这些兴奋剂效应的影响。雄性Wistar大鼠随机接受包括0、0.01、0.1、0.25、1.0、2.0和4.0mg/kg的两种药物剂量。在6个自动实验箱中评估活动情况,每小时记录水平和垂直活动,持续4小时。最初,所有大鼠在5天内对实验箱有相同的接触时间。在随后的药物阶段,适应后的大鼠在每次注射前在实验箱中放置1小时,而非适应的大鼠在相应时间呆在其笼舍中。(+)-苯丙胺刺激了水平活动,尽管在两种情况下,直到注射后第二小时才出现这种效应,但一直持续到第四小时。垂直活动也同样增强,但在适应情况下,第一小时也有显著的刺激效应。对于阿扑吗啡,适应期导致没有显著的刺激效应。未适应的大鼠仅在第一小时对最高剂量在垂直活动上有显著的刺激效应,在第二小时对水平活动有刺激效应。提示环境的相对新奇性影响了对阿扑吗啡的行为反应,但不影响对(+)-苯丙胺的反应。此外,给药时伴随的激活效应应被视为影响药物反应的一个因素。在考虑作用持续时间短的药物时,这种环境因素可能特别重要。