Galanin: a novel therapeutic target for depression, anxiety disorders and drug addiction?

CNS Neurol Disord Drug Targets. 2006 Apr;5(2):225-32. doi: 10.2174/187152706776359600.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / metabolism
  • Anxiety Disorders / physiopathology
  • Biogenic Amines / metabolism
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / physiopathology
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Galanin / agonists
  • Galanin / metabolism*
  • Humans
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism
  • Stress, Psychological / physiopathology
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / metabolism
  • Substance Withdrawal Syndrome / physiopathology
  • Substance-Related Disorders / drug therapy*
  • Substance-Related Disorders / metabolism
  • Substance-Related Disorders / physiopathology

Substances

  • Biogenic Amines
  • Galanin