Berridge Craig W, Stalnaker Thomas A
Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Synapse. 2002 Dec 1;46(3):140-9. doi: 10.1002/syn.10131.
Despite the well-known and potent arousal-enhancing effects of amphetamine (AMPH)-like stimulants, the neurobiological substrates of AMPH-induced arousal have rarely been examined explicitly. Available evidence suggests the possible participation of noradrenergic and/or dopaminergic systems in the arousal-enhancing actions of AMPH-like stimulants. The current studies examined the extent to which low-dose AMPH-induced increases in waking are related to AMPH-induced increases in extracellular norepinephrine (NE) and dopamine (DA) levels within the prefrontal cortex (PFC), as measured by in vivo microdialysis. Vehicle injections elicited brief epochs of waking. Vehicle-induced waking was closely associated with a brief and moderate (50% above baseline) increase in NE levels. DA levels were less sensitive to the arousing actions of vehicle injections, with maximal increases of approximately 25% above baseline observed. 0.15 mg/kg and 0.25 mg/kg AMPH increased time spent awake, which resulted primarily from increases in quiet waking. Although the magnitude of the waking response did not differ substantially between the two doses across time, a trend for a more rapid recovery to baseline waking levels was observed at the higher dose, possibly suggesting the development of a relatively rapid-onset tolerance to the wake-promoting actions of AMPH at this dose. At the 0.15 mg/kg dose, AMPH elicited maximum increases of approximately 175% and 125% above baseline levels for NE and DA, respectively. The time course of AMPH-induced increases in waking closely paralleled the time course of AMPH-induced increases in both NE and DA efflux. These observations are consistent with the hypothesis that both increased DA and NE efflux contribute to the low-dose behavioral effects of AMPH-like stimulants, including the arousal-enhancing actions of these drugs. Additionally, these observations also suggest a possibly greater sensitivity of NE efflux, relative to DA, to moderately arousing conditions including low-dose AMPH-like stimulant administration.
尽管苯丙胺（AMPH）类兴奋剂具有众所周知且强大的增强觉醒作用，但AMPH诱导觉醒的神经生物学底物却很少被明确研究。现有证据表明，去甲肾上腺素能和/或多巴胺能系统可能参与了AMPH类兴奋剂的觉醒增强作用。当前的研究通过体内微透析测量，考察了低剂量AMPH诱导的清醒增加与前额叶皮质（PFC）细胞外去甲肾上腺素（NE）和多巴胺（DA）水平增加之间的关联程度。注射溶剂会引发短暂的清醒期。溶剂诱导的清醒与NE水平短暂且适度（比基线高50%）的增加密切相关。DA水平对溶剂注射的觉醒作用不太敏感，观察到的最大增加幅度约为比基线高25%。0.15mg/kg和0.25mg/kg的AMPH增加了清醒时间，这主要是由于安静清醒时间的增加。尽管两种剂量在不同时间的清醒反应幅度没有显著差异，但在较高剂量下观察到有更快恢复到基线清醒水平的趋势，这可能表明在该剂量下对AMPH的促醒作用相对快速地产生了耐受性。在0.15mg/kg剂量下，AMPH分别使NE和DA比基线水平最大增加约175%和125%。AMPH诱导的清醒增加的时间进程与AMPH诱导的NE和DA流出增加的时间进程密切平行。这些观察结果与以下假设一致，即DA和NE流出增加均促成了AMPH类兴奋剂的低剂量行为效应，包括这些药物的觉醒增强作用。此外，这些观察结果还表明，相对于DA，NE流出对包括低剂量AMPH类兴奋剂给药在内的适度觉醒条件可能更敏感。
