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, 5.72, 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 alpha 4 beta 2 and/or alpha 3 beta 4 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.
Carlson
J
J
Department of Psychology, University of California -- Los Angeles, 405 Hilgard Avenue -- Franz Hall, Los Angeles, CA 90095, USA. jcarlson@ucla.edu
Noguchi
K
K
Ellison
G
G
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003367:Cotinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004525:Efferent Pathways / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D019262:Habenula / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006948:Hyperkinesis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology*; D009538:Nicotine / Q000097:blood / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D016622:Silver Staining; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
D009498:Neurotoxins; D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine