FIGURE 1.

Dopamine as a neuroendocrine–immunomodulator. Schematic representation of DA pathways in CNS and bidirectional DA crosstalk at central and peripheral levels orchestrating the regulation of neuroendocrine, autonomic, lymphoid, and gut axes. Bidirectional circuits linking brain DA to astrocyte and microglial crosstalk are schematically represented. There are three major DA pathways in the brain. The nigrostriatal DA pathway originating in the substantia nigra pars compacta (SNpc, A9) releases DA into the corpus striatum (Str), which governs motor coordination. The mesocortical and mesolimbic DA pathways arise from the ventral tegmental area (VTA, A10), releasing DA into major brain limbic regions, including the nucleus accumbens (Ac), the amygdala (Am), the hippocampus (Hip), and the prefrontal cortex, constituting the mesolimbic–mesocortical reward pathway. Within the hypothalamus (HYP), the tuberoinfundibular DA system modulates the output of releasing factors regulating the hypothalamic–hypophyseal–gonadal (HPG) and hypothalamic–hypophyseal–adrenocortical (HPA) axes, neuropeptides, and hormones, including luteinizing hormone‐releasing hormone (LHRH) and prolactin (PRL), in turn involved in immunomodulation. At peripheral level, DA can communicate with the immune system to modulate its activity, directly through specific receptors in immune organs and cells or indirectly through the peripheral nervous system (PNS), via sympathetic and parasympathetic innervation, neuropeptides, and hormone release. Bidirectional DA crosstalk between CNS and gastrointestinal DA, within the brain–gut axis, also plays roles in modulating microenvironmental cues, including the inflammatory milieu and microbiome homeostasis