A mechanism for interdependent changes in the concentrations of neuromodulators during paradoxical sleep is proposed. According to this mechanism, the release of dopamine in the striatum and modulation of corticostriatal inputs promote disinhibitions via the basal ganglia of cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei, thus initiating paradoxical sleep. Simultaneously, dopamine activates postsynaptic Gi/0-protein-coupled D3 receptors on serotonergic and noradrenergic neurons, thereby promoting depression of their excitation and suppression of their activity. An increase in the concentration of acetylcholine, in turn, leads to an increase in the level of dopamine, serotonin, and noradrenaline, due to activation of nicotinic α-receptors and depolarization of neurons that release these neuromodulators. Serotonergic and noradrenergic neurons enable reciprocal excitation due to activation of Gq/11-protein-coupled 5-HT2 and α1 adrenergic receptors. However, an increase in the activity of serotonergic and noradrenergic cells suppresses paradoxical sleep, first, due to depression of excitation of cholinergic neurons via Gi/0-protein-coupled 5-HT1 and α2 adrenergic receptors. Second, serotonin and noradrenaline suppress the activity of dopaminergic cells by affecting 5-HT2 and α1 adrenergic receptors and by potentiating excitation of GABAergic interneurons projecting onto dopaminergic cells. Owing to the specified changes in the efficiency of inputs to neuromodulatory neurons, opposite changes in concentrations of acetylcholine and dopamine, on the one hand, and serotonin and noradrenaline, on the other hand, lead to alternation of various phases of sleep and wakefulness.