Immunocytochemical evidence for methamphetamine-induced serotonergic axon loss in the rat brain.
Central serotonin (5-HT) axons were visualized by immunocytochemistry to assess both acute and long-lasting changes in innervation density following methamphetamine administration to rats. Two morphologically distinct subtypes of 5-HT axons (fine and beaded) were differentially affected by d-methamphetamine (d-MA); the density of fine serotonergic axons was selectively decreased both 4 hours and 2 weeks after administration of d-MA. Acute depletion of 5-HT from fine axons, but not from beaded axons, was observed in the brains of all rats treated 4 hours previously with either a 100 mg/kg or 15 mg/kg dose of d-MA. Persistent loss of 5-HT axons was observed in 30% of rats treated 1 or 2 weeks previously with doses of d-MA which produce long-term deficits in biochemical markers for 5-HT. In the fraction of animals that exhibited denervation, fine serotonergic fibers were selectively ablated by d-MA, but beaded serotonergic fibers were spared. Thus, d-MA is similar to other amphetamine derivatives (e.g., p-chloroamphetamine, 3,4-methylenedioxyamphetamine) in that it acts selectively upon a morphologically distinct class of 5-HT axons but differs in that it produces long-lasting axon loss in only a fraction of animals. These data provide morphologic evidence of 5-HT axon loss following methamphetamine administration and further confirm the differential vulnerability of a particular morphological subtype of serotonergic axons to the neurotoxic effects of substituted amphetamines.
Axt
K J
KJ
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Molliver
M E
ME
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure*; D003714:Denervation; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000172:deficiency / Q000378:metabolism*; D013194:Staining and Labeling
D012701:Serotonin; D008694:Methamphetamine