NEUROBIOLOGICAL SIMILARITIES IN ANTIDEPRESSANT SLEEP-DEPRIVATION AND PSYCHOSTIMULANT USE - A PSYCHOSTIMULANT THEORY OF ANTIDEPRESSANT SLEEP-DEPRIVATION

This paper attempts to summarize the evidence for the hypothesis that psychostimulant-like neurotransmitter processes within certain regions of the limbic system induce the positive effects of antidepressant sl eep deprivation (SD). Preclinical and human studies indicate similar n eurobiological effects of psychostimulants such as amphetamines, cocai ne and SD. In clinical use, SD and psychostimulants have similar chara cteristics and behavioral effects. Furthermore, acute psychostimulant challenge decreases limbic metabolism in imaging studies, and SD decre ases elevated limbic metabolism in SD responders, indicating that psyc hostimulant-like neurotransmitter release could decrease limbic metabo lism in SD responders. Most antidepressant pharmacotherapies change th e reactivity of the dopamine system, and a decrease of presynaptic dop amine or postsynaptic availability can induce depression. Sleep is acc ompanied by a reduction of catecholamine release and those processes w hich are increased by psychostimulants. It is concluded that a propose d regional postsynaptic deficit in catecholaminergic neurotransmission can be overcome either acutely by enhanced release during SD or psych ostimulant use, or chronically by changes in receptor sensitivity or g ene expression due to antidepressant therapies. A postsynaptic deficit in these areas becomes evident if presynaptic release is reduced in c onditions such as sleep. Therefore, sleep is depressiogenic for predis posed individuals and the reduction of sleep avoids understimulation o f subsensitive postsynaptic processes, which are enhanced by psychosti mulants.