title: Antipsychotic treatment induces alterations in dendrite- and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex.
abstract: BACKGROUND
  Mounting evidence indicates that long-term treatment with antipsychotic medications can alter the morphology and connectivity of cellular processes in the cerebral cortex. The cytoskeleton plays an essential role in the maintenance of cellular morphology and is subject to regulation by intracellular pathways associated with neurotransmitter receptors targeted by antipsychotic drugs.
  
  
  METHODS
  We have examined whether chronic treatment with the antipsychotic drug haloperidol interferes with phosphorylation state and tissue levels of a major dendritic cytoskeleton-stabilizing agent, microtubule-associated protein 2 (MAP2), as well as levels of the dendritic spine-associated protein spinophilin and the synaptic vesicle-associated protein synaptophysin in various regions of the cerebral cortex of rhesus monkeys.
  
  
  RESULTS
  Among the cortical areas examined, the prefrontal, orbital, cingulate, motor, and entorhinal cortices displayed significant decreases in levels of spinophilin, and with the exception of the motor cortex, each of these regions also exhibited increases in the phosphorylation of MAP2. No changes were observed in either spinophilin levels or MAP2 phosphorylation in the primary visual cortex. Also, no statistically significant changes were found in tissue levels of MAP2 or synaptophysin in any of the cortical regions examined.
  
  
  CONCLUSIONS
  Our findings demonstrate that long-term haloperidol exposure alters neuronal cytoskeleton- and spine-associated proteins, particularly in dopamine-rich regions of the primate cerebral cortex, many of which have been implicated in the psychopathology of schizophrenia. The ability of haloperidol to regulate cytoskeletal proteins should be considered in evaluating the mechanisms of both its palliative actions and its side effects.
authors.affiliation: University of Maryland, Department of Oral and Craniofacial Biological Sciences, Room 5-A-12, HHH, 666 W. Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Lidow
authors.forename: Z M
authors.initials: ZM
authors.lastname: Song
authors.forename: S A
authors.initials: SA
authors.lastname: Castner
authors.forename: P B
authors.initials: PB
authors.lastname: Allen
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: P S
authors.initials: PS
authors.lastname: Goldman-Rakic
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D015152:Blotting, Northern; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006220:Haloperidol / Q000633:toxicity*; D008253:Macaca mulatta; D008840:Microfilament Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D016708:Synaptophysin / Q000378:metabolism; D000099273:Neurabins
chemical_list: D014150:Antipsychotic Agents; D004298:Dopamine; D006220:Haloperidol; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D016708:Synaptophysin; D000099273:Neurabins