Relationship between low-dose amphetamine-induced arousal and extracellular norepinephrine and dopamine levels within prefrontal cortex.
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.
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005110:Extracellular Space / Q000187:drug effects*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009638:Norepinephrine / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects
D000697:Central Nervous System Stimulants; D000661:Amphetamine; D004298:Dopamine; D009638:Norepinephrine