Nicotine produces selective degeneration in the medial habenula and fasciculus retroflexus

Nicotine's neurotoxic properties in rats were investigated by administering (-)-nicotine tartrate for 5 days either continuously in doses of 5.01. 5.7 2, 6.44, 7.13, 20.41 and 43.1 mg/kg/day via osmotic minipump or intermitten tly 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 a ll treatment groups except the lowest dose. Within the habenula, the damage was noted in the ventral-medial-most portion of the nucleus which is thoug ht to be dense with the alpha4 beta2 and/or alpha3 beta4 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 resear ch using dopaminergic stimulants, indicate that the habenula may be a weak link in the neurotoxicity seen following stimulant drugs of abuse. (C) 2001 Elsevier Science B.V. All rights reserved.