Effects of catecholamine depletion on alertness and mood in rested and sleep deprived normal volunteers.

Alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, was used to evaluate the physiologic role of central nervous system catecholamines in modulating alertness and mood. Forty healthy males were randomized to one of four conditions: AMPT in a rested condition; AMPT plus 40.5 hours of total sleep deprivation; placebo plus sleep deprivation; or placebo in a rested condition. Repeated measures of alertness and mood revealed that treatment with AMPT or sleep deprivation increased sleepiness, and combined treatment produced greater sleepiness than either treatment alone. In contrast, although combined treatment with AMPT and sleep deprivation led to large increases in negative mood, neither treatment alone produced consistent mood changes. These findings are consistent with the view that sleep deprivation is associated with decreased functional catecholamine neurotransmission. Furthermore, mood effects following sleep deprivation plus AMPT suggest that catecholamines may be involved in mood changes during sleep deprivation.