Chronic treatment with melatonin attenuates serotonergic degeneration in the striatum and olfactory tubercle of zitter mutant rats

Neurosci Lett. 2008 Dec 26;448(2):212-6. doi: 10.1016/j.neulet.2008.10.059. Epub 2008 Nov 1.


The effects of chronic treatment with the antioxidant hormone melatonin on degeneration of serotonergic fibers were studied in the striatum and olfactory tubercle of the zitter rat, which shows a loss-of-function mutation of the glycosylated transmembrane protein attractin. In these animals, serotonergic fibers in the striatum and olfactory tubercle undergo spontaneous and progressive degeneration as a result of abnormal metabolism of reactive oxygen species. Homozygous zitter (zi/zi) rats were provided ad libitum access to drinking water containing melatonin for 9 months (M) after weaning. High-performance liquid chromatography analysis revealed that melatonin treatment significantly increased serotonin in the caudate-putamen, (CPU), nucleus accumbens (NA) and olfactory tubercle (OT). Immunohistochemical staining for serotonin was consistent with the neurochemical data and further demonstrated substantially increased numbers of serotonergic nerve terminals in these areas. Aberrant serotonergic fibers characterized by swollen varicosities (>1 microm in diameter) were observed in the CPU and NA of 10 M zi/zi rats. The number of these fibers decreased after melatonin treatment ended. Furthermore, hyperinnervation of serotonergic fibers was observed in the OT of melatonin-treated zi/zi rats. These results suggest that melatonin protects serotonergic fibers and terminals in zitter rats and/or promotes their neuroplasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Antioxidants / pharmacology
  • Chromatography, High Pressure Liquid
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Immunohistochemistry
  • Male
  • Melatonin / blood
  • Melatonin / pharmacology*
  • Membrane Proteins / genetics
  • Mutation
  • Nerve Degeneration / drug therapy*
  • Nerve Degeneration / genetics*
  • Neuronal Plasticity / drug effects
  • Neurons / drug effects
  • Neurons / metabolism
  • Olfactory Pathways / drug effects*
  • Olfactory Pathways / metabolism
  • Olfactory Pathways / pathology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Rats
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Serotonin / metabolism*


  • Antioxidants
  • Atrn protein, rat
  • Membrane Proteins
  • Reactive Oxygen Species
  • Serotonin
  • Melatonin