Singer G, Armstrong S, Evans B, Burnstock G
Pharmacol Biochem Behav. 1975;3(1 Suppl):91-106.
6-Hydroxydopamine (6-OHDA) has been used extensively to study the effects of catecholamine depletion on feeding and drinking behavior. The results from these experiments are variable and do not clarify the involvement of catecholamines in these behaviors. Guanethidine, which has been used in studies of the peripheral autonomic nervous system, provides an alternative method of catecholamine depletion. In the experiments reviewed here the effects of injections of 6-OHDA and guanethidine into the rat brain on consummatory behavior and temperature regulation have been compared and related to changes in monoamine levels as shown by fluorescence histochemistry. Injections of 6-OHDA into anterior hypothalamic areas have lethal effects on food deprived animals. This effect may be explained in terms of loss of ability to regulate temperature. Animals whose catecholamines were depleted by guanethidine injections into anterior lateral hypothalamus showed a consistent reduction in food and water intake and an elevation of body temperature. Reconciliation of these findings appears difficult. However, a comparative study of the intracranial diffusion patterns of guanethidine and 6-OHDA has revealed marked differences in the extent of diffusion as seen with the fluorescence histochemical method when injected acutely or chronically into the lateral hypothalamus, the substantia nigra or the amygdala of the rat brain. Cannulation damage extended up to 1 mm in diameter. Generalized damage was far greater for 6-OHDA (2 mm) than for guanethidine (0.3 mm). At the doses used guanethidine, but not 6-OHDA caused specific damage to catecholamine-containing neurons up to a distance of at least 3 mm from the cannula tip. Guanethidine was less selective for dopaminergic compared to noradrenergic neurons. These differences between the effects of the two drugs are explained in terms of their unique pharmacological properties and their estimated decay in CNS tissue. An attempt has been made to account for the differences in behavioral data and in particular the variability of the 6-OHDA data in terms of the differences in the type of damage produced by the two drugs and the extent of their diffusion. It is also argued that the different patterns of damage would not easily be distinguished by biochemical analysis, and further, that changes in injection volume and concentration may lead to different damage patterns.
6-羟基多巴胺（6-OHDA）已被广泛用于研究儿茶酚胺耗竭对摄食和饮水行为的影响。这些实验的结果并不一致，未能阐明儿茶酚胺在这些行为中的作用。胍乙啶已用于外周自主神经系统的研究，它提供了一种使儿茶酚胺耗竭的替代方法。在本文回顾的实验中，比较了向大鼠脑内注射6-OHDA和胍乙啶对 consummatory 行为和体温调节的影响，并将其与荧光组织化学所示的单胺水平变化相关联。向前下丘脑区域注射6-OHDA对食物匮乏的动物具有致死作用。这种作用可能是由于调节体温能力的丧失所致。通过向外侧下丘脑前部注射胍乙啶使儿茶酚胺耗竭的动物，其食物和水的摄入量持续减少，体温升高。协调这些发现似乎很困难。然而，一项关于胍乙啶和6-OHDA在颅内扩散模式的比较研究表明，当急性或慢性注射到大鼠脑的外侧下丘脑、黑质或杏仁核时，用荧光组织化学方法观察到的扩散程度存在显著差异。插管损伤直径可达1毫米。6-OHDA（2毫米）造成的广泛损伤远大于胍乙啶（0.3毫米）。在所使用的剂量下，胍乙啶而非6-OHDA对距插管尖端至少3毫米距离内的含儿茶酚胺神经元造成特异性损伤。与去甲肾上腺素能神经元相比，胍乙啶对多巴胺能神经元的选择性较低。这两种药物作用的差异是根据它们独特的药理特性及其在中枢神经系统组织中的估计衰减来解释的。已尝试根据两种药物产生的损伤类型差异及其扩散程度来解释行为数据的差异，特别是6-OHDA数据的变异性。还认为，不同的损伤模式不易通过生化分析区分，而且注射体积和浓度的变化可能导致不同的损伤模式。
