Radioligand binding and immunoautoradiographic evidence for a lack of toxicity to dopaminergic nerve terminals in human cocaine overdose victims

Julie K. Staley, Janet Z. Talbot, Brian J. Ciliax, Gary W. Miller, Allan I. Levey, Mei Ping Kung, Hank F. Kung, Deborah C Mash

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Radioligand binding to and immunolabeling of transport sites associated with monoamine-containing synaptic vesicles affords a novel approach for mapping the integrity of dopaminergic (DAergic) nerve terminals. The present study used [125I]iodovinyltetrabenazine ([125I]TBZ) and a fusion protein antibody directed at the large intraluminal loop of the neuronal vesicular monoamine transporter (hVMAT2-loop) as probes to assess the effects of chronic cocaine use on the integrity of DAergic nerve terminals in the striatum of cocaine fatalities. Visualization of [125I]TBZ binding in human brain revealed a distinct pattern of labeling throughout the rostral-caudal extent of the striatum. Saturation binding of [125I]TBZ in striatal membranes demonstrated a single high affinity site (K(d) = 2.3 ± 0.9 nM and B(max) = 55.5 ± 8.1 pmol/g tissue) with a pharmacological profile (tetrabenazine ≤ iodovinyltetrabenazine > ketanserin ≤ reserpine > haloperidol > GBR 12909) consistent with the specific labeling of hVMAT2. Quantitative in vitro autoradiography demonstrated no significant alteration in the density of [125I]TBZ binding sites in the anterior and posterior sectors of the striatum in cocaine fatalities with and without preterminal excited delirium as compared to drug-free and age-matched control subjects. Similarly, the levels of hVMAT2-loop immunoreactivity were not significantly different across control and cocaine fatality groups. The results demonstrate the lack of an alteration in [125I]TBZ binding sites and hVMAT2 protein in the striatum from a young cohort of cocaine fatalities. Since striatal VMAT2 is primarily associated with DAergic nerve terminals, these results suggest that chronic cocaine use failed to affect the integrity of striatal DAergic nerve terminals.

Original languageEnglish
Pages (from-to)219-229
Number of pages11
JournalBrain Research
Volume747
Issue number2
DOIs
StatePublished - Feb 7 1997

Fingerprint

Cocaine
Corpus Striatum
Tetrabenazine
Binding Sites
Vesicular Monoamine Transport Proteins
Ketanserin
Delirium
Synaptic Vesicles
Reserpine
Haloperidol
Autoradiography
Proteins
Pharmacology
Membranes
Antibodies
Brain
Pharmaceutical Preparations

Keywords

  • autoradiography
  • cocaine
  • human brain
  • striatum
  • vesicular monoamine transporter

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Radioligand binding and immunoautoradiographic evidence for a lack of toxicity to dopaminergic nerve terminals in human cocaine overdose victims. / Staley, Julie K.; Talbot, Janet Z.; Ciliax, Brian J.; Miller, Gary W.; Levey, Allan I.; Kung, Mei Ping; Kung, Hank F.; Mash, Deborah C.

In: Brain Research, Vol. 747, No. 2, 07.02.1997, p. 219-229.

Research output: Contribution to journalArticle

Staley, Julie K. ; Talbot, Janet Z. ; Ciliax, Brian J. ; Miller, Gary W. ; Levey, Allan I. ; Kung, Mei Ping ; Kung, Hank F. ; Mash, Deborah C. / Radioligand binding and immunoautoradiographic evidence for a lack of toxicity to dopaminergic nerve terminals in human cocaine overdose victims. In: Brain Research. 1997 ; Vol. 747, No. 2. pp. 219-229.
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