Immunocytochemical evidence for methamphetamine-induced serotonergic axon loss in the rat brain
Version of Record online: 12 OCT 2004
Copyright © 1991 Wiley-Liss, Inc.
Volume 9, Issue 4, pages 302–313, December 1991
How to Cite
Axt, K. J. and Molliver, M. E. (1991), Immunocytochemical evidence for methamphetamine-induced serotonergic axon loss in the rat brain. Synapse, 9: 302–313. doi: 10.1002/syn.890090405
- Issue online: 12 OCT 2004
- Version of Record online: 12 OCT 2004
- Manuscript Accepted: 18 APR 1991
- Manuscript Received: 5 JAN 1991
- Psychotropic amphetamines;
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.