Persistent alterations in dendrites, spines, and dynorphinergic synapses in the nucleus accumbens shell of rats with neuroleptic-induced dyskinesias.
Chronic treatment of humans or experimental animals with classical neuroleptic drugs can lead to abnormal, tardive movements that persist long after the drugs are withdrawn. A role in these neuroleptic-induced dyskinesias may be played by a structural change in the shell of the nucleus accumbens where the opioid peptide dynorphin is upregulated in treated rats that show vacuous chewing movements (VCMs). The shell of the nucleus accumbens normally contains a dense plexus of dynorphinergic fibers especially in its caudomedial part. After 27 weeks of haloperidol administration and 18 weeks of withdrawal, the immunoreactive labeling of this plexus is intensified when compared with that after vehicle treatment. In addition, medium spiny neurons here show a significant increase in spine density, dendritic branching, and numbers of terminal segments. In the VCM-positive animals, the dendritic surface area is reduced, and dynorphin-positive terminals contact more spines and form more asymmetrical specializations than do those in animals without the syndrome (VCM-negative and vehicle-treated groups). Persistent, neuroleptic-induced oral dyskinesias could therefore be caused by incontrovertible alterations, involving terminal remodeling or sprouting, to the synaptic connectivity of the accumbal shell.
Meredith
G E
GE
Department of Basic Medical Science, University of Missouri-Kansas City, School of Medicine, Kansas City, Missouri 64108-2792, USA. meredithg@umkc.edu
De Souza
I E
IE
Hyde
T M
TM
Tipper
G
G
Wong
M L
ML
Egan
M F
MF
D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity; D001522:Behavior, Animal / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D004399:Dynorphins / Q000378:metabolism*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism* / Q000473:pathology; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D008409:Mastication / Q000187:drug effects; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure
D014150:Antipsychotic Agents; D004399:Dynorphins; D006220:Haloperidol