Nicotine produces selective degeneration in the medial habenula and fasciculus retroflexus

Janice Carlson, Kevin Noguchi, Gaylord Ellison

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54 Scopus citations


Nicotine's neurotoxic properties in rats were investigated by administering (-)-nicotine tartrate for 5 days either continuously in doses of 5.01, 5.72, 6.44, 7.13, 20.41 and 43.1 mg/kg/day via osmotic minipump or intermittently at 11.32 mg/kg/day via one daily subcutaneous injection. As assessed by silver staining, neurotoxicity was seen almost exclusively in the axons of the medial habenula and its output tract, the fasciculus retroflexus, in all treatment groups except the lowest dose. Within the habenula, the damage was noted in the ventral-medial-most portion of the nucleus which is thought to be dense with the α4β2 and/or α3β4 receptor subtypes. Past research has shown the medial habenula to be highly sensitive to the effects of nicotine, and these findings, in conjunction with related research using dopaminergic stimulants, indicate that the habenula may be a weak link in the neurotoxicity seen following stimulant drugs of abuse.

Original languageEnglish
Pages (from-to)127-134
Number of pages8
JournalBrain Research
Issue number1-2
StatePublished - Jul 6 2001


  • Fasciculus retroflexus
  • Habenula
  • Neurotoxicity
  • Nicotine


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