Relationship between low-dose amphetamine-induced arousal and extracellular norepinephrine and dopamine levels within prefrontal cortex

被引:61
作者
Berridge, CW
Stalnaker, TA
机构
[1] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA
关键词
arousal; dopaminergic; noradrenergic; stimulants; waking; sleep; prefrontal cortex; narcolepsy; ADHD;
D O I
10.1002/syn.10131
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:140 / 149
页数:10
相关论文
共 59 条
[1]  
Ahn S, 1999, J NEUROSCI, V19
[2]  
ASTONJONES G, 1981, J NEUROSCI, V1, P876
[3]   Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments [J].
Bassareo, V ;
Di Chiara, G .
NEUROSCIENCE, 1999, 89 (03) :637-641
[4]  
BEKAVAC I, 1995, J PHARMACOL EXP THER, V272, P333
[5]   Relationship between locus coeruleus discharge rates and rates of norepinephrine release within neocortex as assessed by in vivo microdialysis [J].
Berridge, CW ;
Abercrombie, ED .
NEUROSCIENCE, 1999, 93 (04) :1263-1270
[6]   Amphetamine acts within the medial basal forebrain to initiate and maintain alert waking [J].
Berridge, CW ;
O'Neil, J ;
Wifler, K .
NEUROSCIENCE, 1999, 93 (03) :885-896
[7]  
Berridge CW, 1996, J NEUROSCI, V16, P7010
[8]   Amphetamine-induced activation of forebrain EEG is prevented by noradrenergic β-receptor blockade in the halothane-anesthetized rat [J].
Berridge, CW ;
Morris, MF .
PSYCHOPHARMACOLOGY, 2000, 148 (03) :307-313
[9]  
Berridge CW, 1996, J NEUROSCI, V16, P6999
[10]   Differential sensitivity to the wake-promoting actions of norepinephrine within the medial preoptic area and the substantia innominata [J].
Berridge, CW ;
O'Neill, J .
BEHAVIORAL NEUROSCIENCE, 2001, 115 (01) :165-174