Relationship between low-dose amphetamine-induced arousal and extracellular norepinephrine and dopamine levels within prefrontal cortex
Relationship between low-dose amphetamine-induced arousal and extracellular norepinephrine and dopamine levels within prefrontal cortex
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DOI：
10.1002/syn.10131
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发表时间：
2002-12-01
期刊：
影响因子：
2.3
通讯作者：
Stalnaker, TA
中科院分区：
文献类型：
--
作者：
Berridge, CW;Stalnaker, TA
尽管众所周知的和强大的。安非他明（AMPH）样兴奋剂的觉醒增强作用，AMPH诱导的觉醒的神经生物学底物很少被明确检查。现有的证据表明，可能参与的去甲肾上腺素能和/或多巴胺能系统的唤醒增强行动的AMPH样兴奋剂。目前的研究检查了低剂量AMPH诱导的觉醒增加与AMPH诱导的前额叶皮层（PFC）内细胞外去甲肾上腺素（NE）和多巴胺（DA）水平增加的程度，如通过体内微透析测量的。溶媒注射引起短暂的清醒期。溶剂诱导的觉醒与NE水平的短暂和中度（高于基线50%）升高密切相关。DA水平对溶媒注射的激发作用不太敏感，观察到的最大增幅约为基线的25%。0.15 25 mg/kg和0.25 mg/kg AMPH增加了清醒时间，这主要是由于安静清醒时间的增加。尽管两种剂量之间的觉醒反应幅度在时间上没有实质性差异，但在较高剂量下观察到更快恢复至基线觉醒水平的趋势，这可能表明在该剂量下对AMPH的觉醒促进作用产生了相对快速的耐受性。在0.15 mg/kg剂量下，AMPH引起NE和DA分别比基线水平最大增加约175%和125%。AMPH诱导的清醒时间增加的时间过程密切相关的AMPH诱导的NE和DA流出增加的时间过程。这些观察结果是一致的假设，即增加DA和NE流出有助于低剂量的AMPH样兴奋剂的行为效应，包括唤醒增强这些药物的行动。此外，这些观察结果还表明，相对于DA，NE外排对包括低剂量AMPH样兴奋剂给药在内的中度唤醒条件的敏感性可能更高。(C)2002 Wiley-Liss，Inc.
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. (C) 2002 Wiley-Liss, Inc.