Galanin: a novel therapeutic target for depression, anxiety disorders and drug addiction?
Galanin is a neuropeptide synthesized in many neuronal types including brainstem norepinephrine-producing cells of the locus coeruleus and the serotonin-producing neurons of the dorsal raphe nucleus. Galanin inhibits the firing of rodent norepinephrine, serotonin and dopamine neurons and reduces release of these neurotransmitters in forebrain target regions. The distribution of galanin and its receptors and its actions on monoamine signaling has fostered interest in this neuropeptide in the field of behavioral pharmacology and the potential role of galanin in the pathophysiology of neurological diseases such as Alzheimer's disease, epilepsy, stroke, and in psychiatric disorders such as anxiety, depression, and drug addiction, particularly withdrawal. In rodent models, expression of galanin in brain is altered by various stressors, while administration of galanin can modulate anxiety-like responses to stress. Emerging evidence further supports a role for galanin in the mediation of depression-related behaviors in rodents. Recently, galanin agonists have been shown to decrease behavioral signs of opiate withdrawal, which are thought to result from hyperactivation of brain stress pathways. Studies using genetically modified mice suggest that galanin normally plays a protective role against opiate reinforcement and withdrawal. The present article reviews current evidence on a potential role for galanin in modulating stress-related neural pathways and behaviors, and speculates on the therapeutic potential of targeting this galanin system for emotional disorders and opiate addiction.
Holmes
A
A
Laboratory for Integrative Neuroscience, Section on Behavioral Science and Genetics, National Institute of Alcoholism and Alcohol Abuse, National Institutes of Health, Bethesda, Maryland 20892, USA. holmesan@mail.nih.gov
Picciotto
M R
MR
D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D001679:Biogenic Amines / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D019004:Galanin / Q000819:agonists / Q000378:metabolism*; D006801:Humans; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D001679:Biogenic Amines; D019004:Galanin