Biochemical adaptations in the mesolimbic dopamine system in response to heroin self‐administration

Biochemical adaptations in the mesolimbic dopamine system in response to heroin... Previous studies have shown that chronic, forced exposure to opiates produces specific biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc). The functional consequences of these adaptations have been hypothesized to contribute to certain motivational aspects of drug addiction. In this study, the possibility that similar adaptations could occur in response to intermittent heroin self‐administration was tested by comparing homogenates of VTA and NAc from rats self‐administering heroin, rats receiving yoked injections of heroin, and rats receiving yoked injections of saline (controls). Tyrosine hydroxylase (TH) immunoreactivity was increased (31–38%) in the VTA and decreased (11%) in the NAc of heroin‐exposed rats relative to controls. Heroin exposure also increased cAMP‐dependent protein kinase (PKA) activity in both particulate (19–27%) and soluble (17–20%) fractions of the NAc, and decreased (16–17%) the level of Giα, immunoreactivity in this brain region. In contrast, no significant biochemical changes were found in the substantia nigra or caudate‐puta‐men, indicating a selective effect on the mesolimbic dopamine system. Overall, adapta‐tions in the VTA and NAc of heroin‐exposed rats were similar to, but generally smaller in magnitude than, adaptations produced by chronic morphine administration. However, in contrast to morphine‐treated animals, heroin‐exposed animals failed to display overt signs of opiate physical dependence, suggesting that adaptations in motivational systems may occur more readily than adaptations in brain regions associated with physical dependence. © 1995 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

Biochemical adaptations in the mesolimbic dopamine system in response to heroin self‐administration

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Publisher
Wiley
Copyright
Copyright © 1995 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
DOI
10.1002/syn.890210405
Publisher site
See Article on Publisher Site

Abstract

Previous studies have shown that chronic, forced exposure to opiates produces specific biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc). The functional consequences of these adaptations have been hypothesized to contribute to certain motivational aspects of drug addiction. In this study, the possibility that similar adaptations could occur in response to intermittent heroin self‐administration was tested by comparing homogenates of VTA and NAc from rats self‐administering heroin, rats receiving yoked injections of heroin, and rats receiving yoked injections of saline (controls). Tyrosine hydroxylase (TH) immunoreactivity was increased (31–38%) in the VTA and decreased (11%) in the NAc of heroin‐exposed rats relative to controls. Heroin exposure also increased cAMP‐dependent protein kinase (PKA) activity in both particulate (19–27%) and soluble (17–20%) fractions of the NAc, and decreased (16–17%) the level of Giα, immunoreactivity in this brain region. In contrast, no significant biochemical changes were found in the substantia nigra or caudate‐puta‐men, indicating a selective effect on the mesolimbic dopamine system. Overall, adapta‐tions in the VTA and NAc of heroin‐exposed rats were similar to, but generally smaller in magnitude than, adaptations produced by chronic morphine administration. However, in contrast to morphine‐treated animals, heroin‐exposed animals failed to display overt signs of opiate physical dependence, suggesting that adaptations in motivational systems may occur more readily than adaptations in brain regions associated with physical dependence. © 1995 Wiley‐Liss, Inc.

Journal

SynapseWiley

Published: Dec 1, 1995

References

  • Heroin and cocaine intravenous self‐administration in rats: Mediation by separate neural systems
    Ettenberg, Ettenberg; Pettit, Pettit; Bloom, Bloom; Koob, Koob
  • Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system
    Ortiz, Ortiz; Fitzgerald, Fitzgerald; Charlton, Charlton; Lane, Lane; Trevisan, Trevisan; Guitart, Guitart; Shoemaker, Shoemaker; Duman, Duman; Nestler, Nestler
  • Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self‐administration in rats
    Pettit, Pettit; Ettenberg, Ettenberg; Bloom, Bloom; Koob, Koob
  • Molecular mechanisms of drug reinforcement and addiction
    Self, Self; Nestler, Nestler
  • Blockade of nucleus accumbens opiate receptors attenuates intravenous heroin reward in the rat
    Vaccarino, Vaccarino; Bloom, Bloom; Koob, Koob

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