title: In vivo evidence for low striatal vesicular monoamine transporter 2 (VMAT2) availability in cocaine abusers.
abstract: OBJECTIVE
  Positron emission tomography (PET) imaging studies in cocaine abusers have shown that low dopamine release in the striatum following an amphetamine challenge is associated with higher relapse rates. One possible mechanism that might lead to lower amphetamine-induced dopamine release is low availability of dopamine storage vesicles in the presynaptic terminals for release. Consistent with this hypothesis, postmortem studies have shown low levels of vesicular monoamine transporter, type 2 (VMAT2), the membrane protein that regulates the size of the vesicular dopamine pool, in cocaine abusers relative to healthy subjects. To confirm the postmortem findings, the authors used PET and the VMAT2 radioligand [¹¹C]-(+)-dihydrotetrabenazine (DTBZ) to assess the in vivo VMAT2 availability in a group of 12 recently abstinent cocaine-dependent subjects and matched healthy comparison subjects.
  
  
  METHODS
  [¹¹C]DTBZ nondisplaceable binding potential (BP(ND)) was measured by kinetic analysis using the arterial input function or, if arterial input was unavailable, by the simplified reference tissue method.
  
  
  RESULTS
  [¹¹C]DTBZ BP(ND) was significantly lower in the cocaine abusers than in the comparison subjects in the limbic striatum (10.0% lower), associative striatum (-13.4%), and sensorimotor striatum (-11.5%).
  
  
  CONCLUSIONS
  The results of this in vivo PET study confirm previous in vitro reports of low VMAT2 availability in the striatum of cocaine abusers. It also suggests a compensatory down-regulation of the dopamine storage vesicles in response to chronic cocaine abuse and/or a loss of dopaminergic terminals. Further research is necessary to understand the clinical relevance of this observation to relapse and outcome in abstinent cocaine abusers.
authors.affiliation: Department of Radiology, University of Pittsburgh, USA. narendranr@upmc.edu
authors.forename: Rajesh
authors.initials: R
authors.lastname: Narendran
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lopresti
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.forename: Neale Scott
authors.initials: NS
authors.lastname: Mason
authors.forename: Michael
authors.initials: M
authors.lastname: Himes
authors.forename: Maureen A
authors.initials: MA
authors.lastname: May
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Daley
authors.forename: Julie C
authors.initials: JC
authors.lastname: Price
authors.forename: Chester A
authors.initials: CA
authors.lastname: Mathis
authors.forename: W Gordon
authors.initials: WG
authors.lastname: Frankle
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D013747:Tetrabenazine / Q000031:analogs & derivatives; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine