D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims

Deborah C Mash, Julie K. Staley

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Cocaine is thought to be addictive because chronic use leads to molecular adaptations within the mesolimbic dopamine (DA) circuitry, which affects motivated behavior and emotion. Although the reinforcing effects of cocaine are mediated primarily by blockade of DA uptake, reciprocal signaling between DA and endogenous opioids has important implications for understanding cocaine dependence. We have used in vitro autoradiography and ligand binding to map D3 DA and kappa opioid receptors in the human brains of cocaine-overdose victims. The number of D3 binding sites was increased one- to threefold over the nucleus accumbens and ventromedial sectors of the caudate and putamen from cocaine-overdose victims, as compared to age-matched and drug-free control subjects. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were increased sixfold in cocaine-overdose victims over control values, suggesting that cocaine exposure also affects the expression of D3 receptor mRNA. The number of kappa opioid receptors in the nucleus accumbens and other corticolimbic areas from cocaine fatalities was increased twofold as compared to control values. Cocaine-overdose victims exhibiting preterminal excited delirium had a selective upregulation of kappa receptors measured also in the amygdala. Understanding the complex regulatory profiles of DA and opioid synaptic markers that occur with chronic misuse of cocaine may suggest multitarget strategies for treating cocaine dependence.

Original languageEnglish
Pages (from-to)507-522
Number of pages16
JournalAnnals of the New York Academy of Sciences
Volume877
DOIs
StatePublished - Aug 5 1999

Fingerprint

kappa Opioid Receptor
Cocaine
Dopamine
Brain
Nucleus Accumbens
Cocaine-Related Disorders
Opioid Analgesics
Cyclophilins
Alteration
Messenger RNA
Delirium
Drug and Narcotic Control
Putamen
Amygdala
Autoradiography
Emotions
Up-Regulation
Binding Sites
Ligands

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims. / Mash, Deborah C; Staley, Julie K.

In: Annals of the New York Academy of Sciences, Vol. 877, 05.08.1999, p. 507-522.

Research output: Contribution to journalArticle

@article{d3cceafee7284f7d96864a4f46a961c2,
title = "D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims",
abstract = "Cocaine is thought to be addictive because chronic use leads to molecular adaptations within the mesolimbic dopamine (DA) circuitry, which affects motivated behavior and emotion. Although the reinforcing effects of cocaine are mediated primarily by blockade of DA uptake, reciprocal signaling between DA and endogenous opioids has important implications for understanding cocaine dependence. We have used in vitro autoradiography and ligand binding to map D3 DA and kappa opioid receptors in the human brains of cocaine-overdose victims. The number of D3 binding sites was increased one- to threefold over the nucleus accumbens and ventromedial sectors of the caudate and putamen from cocaine-overdose victims, as compared to age-matched and drug-free control subjects. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were increased sixfold in cocaine-overdose victims over control values, suggesting that cocaine exposure also affects the expression of D3 receptor mRNA. The number of kappa opioid receptors in the nucleus accumbens and other corticolimbic areas from cocaine fatalities was increased twofold as compared to control values. Cocaine-overdose victims exhibiting preterminal excited delirium had a selective upregulation of kappa receptors measured also in the amygdala. Understanding the complex regulatory profiles of DA and opioid synaptic markers that occur with chronic misuse of cocaine may suggest multitarget strategies for treating cocaine dependence.",
author = "Mash, {Deborah C} and Staley, {Julie K.}",
year = "1999",
month = "8",
day = "5",
doi = "10.1111/j.1749-6632.1999.tb09286.x",
language = "English",
volume = "877",
pages = "507--522",
journal = "Annals of the New York Academy of Sciences",
issn = "0077-8923",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims

AU - Mash, Deborah C

AU - Staley, Julie K.

PY - 1999/8/5

Y1 - 1999/8/5

N2 - Cocaine is thought to be addictive because chronic use leads to molecular adaptations within the mesolimbic dopamine (DA) circuitry, which affects motivated behavior and emotion. Although the reinforcing effects of cocaine are mediated primarily by blockade of DA uptake, reciprocal signaling between DA and endogenous opioids has important implications for understanding cocaine dependence. We have used in vitro autoradiography and ligand binding to map D3 DA and kappa opioid receptors in the human brains of cocaine-overdose victims. The number of D3 binding sites was increased one- to threefold over the nucleus accumbens and ventromedial sectors of the caudate and putamen from cocaine-overdose victims, as compared to age-matched and drug-free control subjects. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were increased sixfold in cocaine-overdose victims over control values, suggesting that cocaine exposure also affects the expression of D3 receptor mRNA. The number of kappa opioid receptors in the nucleus accumbens and other corticolimbic areas from cocaine fatalities was increased twofold as compared to control values. Cocaine-overdose victims exhibiting preterminal excited delirium had a selective upregulation of kappa receptors measured also in the amygdala. Understanding the complex regulatory profiles of DA and opioid synaptic markers that occur with chronic misuse of cocaine may suggest multitarget strategies for treating cocaine dependence.

AB - Cocaine is thought to be addictive because chronic use leads to molecular adaptations within the mesolimbic dopamine (DA) circuitry, which affects motivated behavior and emotion. Although the reinforcing effects of cocaine are mediated primarily by blockade of DA uptake, reciprocal signaling between DA and endogenous opioids has important implications for understanding cocaine dependence. We have used in vitro autoradiography and ligand binding to map D3 DA and kappa opioid receptors in the human brains of cocaine-overdose victims. The number of D3 binding sites was increased one- to threefold over the nucleus accumbens and ventromedial sectors of the caudate and putamen from cocaine-overdose victims, as compared to age-matched and drug-free control subjects. D3 receptor/cyclophilin mRNA ratios in the nucleus accumbens were increased sixfold in cocaine-overdose victims over control values, suggesting that cocaine exposure also affects the expression of D3 receptor mRNA. The number of kappa opioid receptors in the nucleus accumbens and other corticolimbic areas from cocaine fatalities was increased twofold as compared to control values. Cocaine-overdose victims exhibiting preterminal excited delirium had a selective upregulation of kappa receptors measured also in the amygdala. Understanding the complex regulatory profiles of DA and opioid synaptic markers that occur with chronic misuse of cocaine may suggest multitarget strategies for treating cocaine dependence.

UR - http://www.scopus.com/inward/record.url?scp=0032588736&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032588736&partnerID=8YFLogxK

U2 - 10.1111/j.1749-6632.1999.tb09286.x

DO - 10.1111/j.1749-6632.1999.tb09286.x

M3 - Article

C2 - 10415668

AN - SCOPUS:0032588736

VL - 877

SP - 507

EP - 522

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -