{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Galanin (GAL) is a widely distributed neuropeptide that modulates a diverse array of physiological and behavioral processes through its interactions with multiple G protein–coupled receptors. Studies have demonstrated that GAL‐expressing neurons are critical for social and reproductive behaviors; for example, a subset of galanin neurons in the medial preoptic area is essential for proper parental care and suppression of pup‐directed aggression (1). GAL has also been implicated in mood regulation, with gene‐based analyses linking variations in the galanin gene to major depressive disorder and altered serotonergic signaling (2). In the context of energy homeostasis, galanin is one of several neuropeptides integrated into leptin‐responsive hypothalamic circuits that regulate feeding behaviors, and galanin expression in leptin receptor–expressing neurons suggests a role in modulating appetite and metabolism (3,12)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the cellular level, GAL exerts its effects via at least three receptor subtypes (GALR1, GALR2, and GALR3). Biochemical studies have shown that, in contrast to its related peptide GALP that preferentially binds GALR2 (4), galanin itself is relatively non‐selective and can engage multiple receptor pathways. Functional studies in genetically modified mice highlight receptor‐specific roles for GAL. In several models, deficiency of GALR1 leads to increased anxiety‐like behavior, heightened seizure susceptibility, aberrant nociceptive responses, and neuroendocrine disturbances—findings that point to an anticonvulsant and anxiolytic function for GAL mediated via GALR1 (6,7,9,13,16). Conversely, activation of GALR2 has been associated with neuroprotective actions in hippocampal neurons and promotion of cell survival against excitotoxic insults (8), although knockout studies of GALR2 have yielded little overt phenotype, implying possible redundancy or compensatory mechanisms (15)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its roles in mood, seizure, and energy regulation, galanin influences pain processing in the peripheral nervous system. Upregulation of galanin in dorsal root ganglia after nerve injury appears to be involved in modulating nociceptive transmission—where stimulation of GAL1 receptors on dorsal horn neurons produces antinociception while presynaptic activation of GAL2 receptors may contribute to pronociceptive effects (6,13). GAL also counteracts the physical manifestations of opiate withdrawal through suppression of locus coeruleus activation (10) and participates in nerve–tumor interactions by promoting neuritogenesis and cancer invasion via GALR2‐mediated signaling (11). Finally, genetic association studies have linked specific galanin haplotypes not only with anxiety but also with vulnerability to alcoholism, suggesting a broader role for GAL in stress‐related and addictive disorders (14).\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted neuromodulatory actions of galanin in both the central and peripheral nervous systems, with receptor‐dependent effects that hold promise for therapeutic targeting in conditions ranging from mood disorders, epilepsy, and chronic pain to addiction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zheng Wu, Anita E Autry, Joseph F Bergan, et al. 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