Brien S E, Wilson E, Heaton J P, Adams M A
Department of Pharmacology and Toxicology, Queen's University, Kingston, Canada.
Int J Impot Res. 2000 Apr;12(2):91-6. doi: 10.1038/sj.ijir.3900488.
Several animal models are currently used in erectile (dys)function research; these models fail to account for the conditions involving the more spontaneous erections in humans. Recently, we observed an increase in the number of 'spontaneously' occurring erections in rats with previous exposure to apomorphine (APO), a centrally acting drug that initiates penile erections and yawns. Based on this observation, we designed a series of experiments to characterize the development of enhanced, non-apomorphine-induced erections or 'spontaneous' erectile responses to vehicle administration in rats with previous exposure to APO. We further examined the effects of castration on these conditioned erections. Naive (ie never received APO) rats were administered vehicle (1 ml/kg saline) to determine the frequency of baseline erections and yawns. An alternating series of APO (80 microg/kg s.c.) and vehicle administrations were performed over several days and subsequent erectile and yawning responses were recorded. Following 3 sets of 3 APO administrations (with vehicle administered between sets), and the 3rd vehicle administration, these rats were then surgically castrated and allowed 30 days to recover. Following this, APO was administered 3 times to determine erectile and yawning responses post-castration, followed by vehicle administration to determine the effects of castration on conditioned APO responses. The major findings were: (1) that although naive rats had a basal spontaneous erectile response (0.75 +/- 0.88; 4 of 8 rats with at least one erection), repetitive administration (up to 22 treatments) of the central initiator apomorphine significantly increased the number of erections (1.8 +/- 0.7; 7 of 8 rats with at least one erection) and yawning (2.5 +/- 2.47) responses to vehicle administration; and (2) both spontaneous yawning and erectile responses were found to be androgen dependent since castration dramatically lowered the number of erections (0.13 +/- 0.35; 1 of 8 rats with at least one erection) and yawns (0). Therefore, this method of producing erections without a pharmacological manipulation provides an additional animal model which can be used in conjunction with the APO-induced erections in characterizing the physiology and pathophysiology of erectile function in conscious rats.
目前,几种动物模型被用于勃起(功能障碍)研究;但这些模型未能考虑到涉及人类更自然勃起的情况。最近,我们观察到先前接触过阿扑吗啡(APO)的大鼠“自然”勃起的数量有所增加,阿扑吗啡是一种能引发阴茎勃起和打哈欠的中枢作用药物。基于这一观察结果,我们设计了一系列实验,以表征在先前接触过APO的大鼠中,增强的、非阿扑吗啡诱导的勃起或对赋形剂给药的“自然”勃起反应的发展情况。我们进一步研究了去势对这些条件性勃起的影响。对未经处理(即从未接受过APO)的大鼠给予赋形剂(1 ml/kg生理盐水),以确定基线勃起和打哈欠的频率。在几天内交替进行阿扑吗啡(80 μg/kg皮下注射)和赋形剂给药,并记录随后的勃起和打哈欠反应。在进行3组每组3次阿扑吗啡给药(组间给予赋形剂)以及第3次赋形剂给药后,然后对这些大鼠进行手术去势,并让其恢复30天。在此之后,给予3次阿扑吗啡以确定去势后的勃起和打哈欠反应,随后给予赋形剂以确定去势对条件性阿扑吗啡反应的影响。主要研究结果如下:(1)尽管未经处理的大鼠有基础自然勃起反应(0.75±0.88;8只大鼠中有4只至少有一次勃起),但重复给予(最多22次处理)中枢启动剂阿扑吗啡显著增加了对赋形剂给药的勃起次数(1.8±0.7;8只大鼠中有7只至少有一次勃起)和打哈欠次数(2.5±2.47);(2)发现自然打哈欠和勃起反应均依赖雄激素,因为去势显著降低了勃起次数(0.13±0.35;8只大鼠中有1只至少有一次勃起)和打哈欠次数(0)。因此,这种无需药理学操作即可产生勃起的方法提供了一种额外的动物模型,可与阿扑吗啡诱导的勃起一起用于表征清醒大鼠勃起功能的生理学和病理生理学。