Abstract

Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.

Original languageEnglish (US)
Pages (from-to)744-755
Number of pages12
JournalBehavioral Neuroscience
Volume129
Issue number6
DOIs
StatePublished - Dec 1 2015

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Heroin
Motivation
Opioid Analgesics
Pharmaceutical Preparations
Drug Overdose
mu Opioid Receptor
Receptor-Interacting Protein Serine-Threonine Kinases
Self Administration
Dopamine D2 Receptors
Nucleus Accumbens
Prefrontal Cortex
Reward
Accidents
Prescriptions
Neurotransmitter Agents
Cause of Death
Hippocampus
Dopamine
Proteins
Brain

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Cite this

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title = "Low expression of D2R and wntless correlates with high motivation for heroin",
abstract = "Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the {"}addiction-like{"} behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.",
author = "Tacelosky, {Diana M.} and Alexander, {Danielle N.} and Megan Morse and Andras Hajnal and Arthur Berg and Robert Levenson and Grigson-Kennedy, {Patricia {"}Sue{"}}",
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Low expression of D2R and wntless correlates with high motivation for heroin. / Tacelosky, Diana M.; Alexander, Danielle N.; Morse, Megan; Hajnal, Andras; Berg, Arthur; Levenson, Robert; Grigson-Kennedy, Patricia "Sue".

In: Behavioral Neuroscience, Vol. 129, No. 6, 01.12.2015, p. 744-755.

Research output: Contribution to journalArticle

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T1 - Low expression of D2R and wntless correlates with high motivation for heroin

AU - Tacelosky, Diana M.

AU - Alexander, Danielle N.

AU - Morse, Megan

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AU - Berg, Arthur

AU - Levenson, Robert

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N2 - Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.

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