España Rodrigo A, Plahn Stacey, Berridge Craig W
Department of Psychology, University of Wisconsin, 1202 W. Johnson St., Madison, WI 53706-1611, USA.
Brain Res. 2002 Jul 12;943(2):224-36. doi: 10.1016/s0006-8993(02)02653-7.
The hypocretins/orexins modulate behavioral state as well as a variety of state-dependent behaviors. Levels of hypocretin-1 and prepro-hypocretin mRNA vary in a circadian fashion, suggesting that hypocretin neurotransmission may vary across the circadian cycle. To better assess the circadian dependency of the behavioral actions of hypocretin-1, the behavioral effects of intracerebroventricular hypocretin-1 administration (3.0 nmol/2 microl) were examined at differing portions of the circadian cycle, when animals display either low levels of waking (light-period) or high levels of waking (dark-period). In addition, mediation analyses were conducted to better assess the contribution of the wake-promoting actions to other behavioral actions of hypocretin-1. During the light-period, hypocretin-1 administration increased time spent awake, grooming, feeding, locomotor activity and chewing of inedible material, a stress-related behavior. Comparable effects of hypocretin-1 on time spent awake, locomotor activity and the chewing of inedible material were observed during the dark-period. In contrast, hypocretin-1-induced feeding and drinking appeared largely circadian-dependent: hypocretin-1 had minimal effects on these behaviors during the dark-period. Hypocretin-1-induced increases in grooming appeared moderately circadian-dependent. These observations suggest that the previously described ability of hypocretin to increase feeding and drinking during the light-period may reflect, at least in part, a general behavioral activation associated with waking. Results from the mediation analyses support these conclusions, indicating that hypocretin-1-induced increases in waking largely account for hypocretin-1-induced increases in feeding and drinking. Additionally, given that chewing and grooming are stress-related behaviors, these observations provide further support for a possible function of HCRT in stress.
下丘脑泌素/食欲素调节行为状态以及多种与状态相关的行为。下丘脑泌素-1和前体下丘脑泌素mRNA的水平呈昼夜节律变化，这表明下丘脑泌素神经传递可能在昼夜周期中有所不同。为了更好地评估下丘脑泌素-1行为作用的昼夜依赖性，我们在昼夜周期的不同时间段，即动物处于低觉醒水平（光照期）或高觉醒水平（黑暗期）时，检测了脑室内注射下丘脑泌素-1（3.0 nmol/2微升）的行为效应。此外，进行了中介分析，以更好地评估促觉醒作用对下丘脑泌素-1其他行为作用的贡献。在光照期，注射下丘脑泌素-1增加了清醒时间、梳理毛发、进食、运动活动以及咀嚼不可食用物质（一种与应激相关的行为）的时间。在黑暗期观察到下丘脑泌素-1对清醒时间、运动活动和咀嚼不可食用物质有类似的影响。相比之下，下丘脑泌素-1诱导的进食和饮水在很大程度上似乎依赖于昼夜节律：下丘脑泌素-1在黑暗期对这些行为的影响最小。下丘脑泌素-1诱导的梳理毛发增加在一定程度上依赖于昼夜节律。这些观察结果表明，先前描述的下丘脑泌素在光照期增加进食和饮水的能力可能至少部分反映了与清醒相关的一般行为激活。中介分析的结果支持了这些结论，表明下丘脑泌素-1诱导的清醒增加在很大程度上解释了下丘脑泌素-1诱导的进食和饮水增加。此外，鉴于咀嚼和梳理毛发是与应激相关的行为，这些观察结果进一步支持了下丘脑泌素释放肽在应激中可能发挥的作用。
