TY - JOUR
T1 - Biochemical adaptations in the mesolimbic dopamine system in response to heroin self‐administration
AU - Self, D. W.
AU - McClenahan, A. W.
AU - Beitner-Johnson, D.
AU - Terwilliger, R. Z.
AU - Nestler, E. J.
PY - 1995/12
Y1 - 1995/12
N2 - 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.
AB - 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.
KW - Cyclic AMP‐dependent protein kinase
KW - G protein
KW - G protein
KW - Glial fibrillary acidic protein
KW - Neurofilament protein
KW - Opiate
KW - Opioid
KW - Tyrosine hydroxylase
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U2 - 10.1002/syn.890210405
DO - 10.1002/syn.890210405
M3 - Article
C2 - 8869161
AN - SCOPUS:0029620705
SN - 0887-4476
VL - 21
SP - 312
EP - 318
JO - Synapse
JF - Synapse
IS - 4
ER -