Repeated exposure to methamphetamine causes long-lasting presynaptic corticostriatal depression that is renormalized with drug readministration.
Addiction-associated behaviors such as drug craving and relapse are hypothesized to result from synaptic changes that persist long after withdrawal and are renormalized by drug reinstatement, although such chronic synaptic effects have not been identified. We report that exposure to the dopamine releaser methamphetamine for 10 days elicits a long-lasting (>4 month) depression at corticostriatal terminals that is reversed by methamphetamine readministration. Both methamphetamine-induced chronic presynaptic depression and the drug's selective renormalization in drug-experienced animals are independent of corresponding long-term changes in synaptic dopamine release but are due to alterations in D1 dopamine and cholinergic receptor systems. These mechanisms might provide a synaptic basis that underlies addiction and habit learning and their long-term maintenance.
Bamford
Nigel S
NS
Department of Neurology, University of Washington, Seattle, WA 98105, USA. bamford@u.washington.edu
Zhang
Hui
H
Joyce
John A
JA
Scarlis
Christine A
CA
Hanan
Whitney
W
Wu
Nan-Ping
NP
André
Véronique M
VM
Cohen
Rachel
R
Cepeda
Carlos
C
Levine
Michael S
MS
Harleton
Erin
E
Sulzer
David
D
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D008694:Methamphetamine