The basis for the definition of a system as a synaptic system is its ability to induce EPSPs via ionotropic receptors/sodium channels or IPSPs via ionotropic receptors/chloride channels. Ionotropic receptors/sodium channels are present in the glutamatergic and acetylcholinergic system. The GABA and glycine systems have ionotropic receptors/chloride channels. The major synaptic systems of the mammalian brain are GABA- and glutamatergic systems. The physiological role of paracrine or diffuse neuromodulatory nonsynaptic systems is described by the example of dopaminergic and serotonergic systems. The mesolimbic and mesocortical dopaminergic systems form emotionally positive states. Nigrostriatal dopaminergic systems control behavior by modification of glutamate- and GABAergic ionotropic receptors of spiny neurons of neostriatum by a transduction signal. Description of the anatomical pathways of interaction of dopaminergic systems suggests that mesolimbic dopaminergic system induces purposeful emotionally motivated behavior via the nucleus accumbens, substantia nigra pars reticulata, and ventral pallidum. The physiological role of the serotonergic paracrine system is the formation of emotionally negative states. The antidepressant effect of tricyclic antidepressants depends on an initially negative state of animals, develops via interaction with the dopaminergic system, and, finally, is determined by the activation of the dopaminergic system of the brain.