Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration.

E. F. Schmidt, M. A. Sutton, C. A. Schad, D. A. Karanian, E. S. Brodkin, D. W. Self

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylase (TH) levels in the mesolimbic dopamine system. In this study, 12 d of cocaine self-administration in rats (4 hr/d) reduced TH immunoreactivity by 29% in the nucleus accumbens (NAc) shell, but not core, after a 1 week withdrawal period. In contrast, TH immunoreactivity in the NAc was completely restored in animals that experienced extinction training (4 hr/d) during the same withdrawal period. Extinction training also increased TH levels in the ventral tegmental area (VTA) by 45%, whereas TH was not altered in the VTA by cocaine withdrawal alone. Thus, extinction-induced normalization of NAc TH levels could involve increased TH synthesis, stability, and/or transport from the VTA to the NAc. A similar extinction training regimen failed to alter TH levels in the NAc or VTA of rats trained to self-administer sucrose pellets, indicating that TH regulation in cocaine-trained animals is not a generalized effect of extinction learning per se. Rather, these data suggest that neuroadaptative responses during cocaine withdrawal ultimately are determined by a complex interaction between chronic drug exposure and drug-seeking experience. The ability of extinction training to restore NAc TH levels is hypothesized to accelerate recovery from dopamine depletion and anhedonia during cocaine withdrawal.

Original languageEnglish (US)
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume21
Issue number7
StatePublished - 2001

Fingerprint

Self Administration
Tyrosine 3-Monooxygenase
Cocaine
Nucleus Accumbens
Ventral Tegmental Area
Dopamine
Psychological Extinction
Anhedonia
Aptitude
Street Drugs
Pharmaceutical Preparations
Sucrose
Learning

Cite this

Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration. / Schmidt, E. F.; Sutton, M. A.; Schad, C. A.; Karanian, D. A.; Brodkin, E. S.; Self, D. W.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 21, No. 7, 2001.

Research output: Contribution to journalArticle

@article{d5cad46b69ae41ce9744acaac7eb1a31,
title = "Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration.",
abstract = "Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylase (TH) levels in the mesolimbic dopamine system. In this study, 12 d of cocaine self-administration in rats (4 hr/d) reduced TH immunoreactivity by 29{\%} in the nucleus accumbens (NAc) shell, but not core, after a 1 week withdrawal period. In contrast, TH immunoreactivity in the NAc was completely restored in animals that experienced extinction training (4 hr/d) during the same withdrawal period. Extinction training also increased TH levels in the ventral tegmental area (VTA) by 45{\%}, whereas TH was not altered in the VTA by cocaine withdrawal alone. Thus, extinction-induced normalization of NAc TH levels could involve increased TH synthesis, stability, and/or transport from the VTA to the NAc. A similar extinction training regimen failed to alter TH levels in the NAc or VTA of rats trained to self-administer sucrose pellets, indicating that TH regulation in cocaine-trained animals is not a generalized effect of extinction learning per se. Rather, these data suggest that neuroadaptative responses during cocaine withdrawal ultimately are determined by a complex interaction between chronic drug exposure and drug-seeking experience. The ability of extinction training to restore NAc TH levels is hypothesized to accelerate recovery from dopamine depletion and anhedonia during cocaine withdrawal.",
author = "Schmidt, {E. F.} and Sutton, {M. A.} and Schad, {C. A.} and Karanian, {D. A.} and Brodkin, {E. S.} and Self, {D. W.}",
year = "2001",
language = "English (US)",
volume = "21",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "7",

}

TY - JOUR

T1 - Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration.

AU - Schmidt, E. F.

AU - Sutton, M. A.

AU - Schad, C. A.

AU - Karanian, D. A.

AU - Brodkin, E. S.

AU - Self, D. W.

PY - 2001

Y1 - 2001

N2 - Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylase (TH) levels in the mesolimbic dopamine system. In this study, 12 d of cocaine self-administration in rats (4 hr/d) reduced TH immunoreactivity by 29% in the nucleus accumbens (NAc) shell, but not core, after a 1 week withdrawal period. In contrast, TH immunoreactivity in the NAc was completely restored in animals that experienced extinction training (4 hr/d) during the same withdrawal period. Extinction training also increased TH levels in the ventral tegmental area (VTA) by 45%, whereas TH was not altered in the VTA by cocaine withdrawal alone. Thus, extinction-induced normalization of NAc TH levels could involve increased TH synthesis, stability, and/or transport from the VTA to the NAc. A similar extinction training regimen failed to alter TH levels in the NAc or VTA of rats trained to self-administer sucrose pellets, indicating that TH regulation in cocaine-trained animals is not a generalized effect of extinction learning per se. Rather, these data suggest that neuroadaptative responses during cocaine withdrawal ultimately are determined by a complex interaction between chronic drug exposure and drug-seeking experience. The ability of extinction training to restore NAc TH levels is hypothesized to accelerate recovery from dopamine depletion and anhedonia during cocaine withdrawal.

AB - Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylase (TH) levels in the mesolimbic dopamine system. In this study, 12 d of cocaine self-administration in rats (4 hr/d) reduced TH immunoreactivity by 29% in the nucleus accumbens (NAc) shell, but not core, after a 1 week withdrawal period. In contrast, TH immunoreactivity in the NAc was completely restored in animals that experienced extinction training (4 hr/d) during the same withdrawal period. Extinction training also increased TH levels in the ventral tegmental area (VTA) by 45%, whereas TH was not altered in the VTA by cocaine withdrawal alone. Thus, extinction-induced normalization of NAc TH levels could involve increased TH synthesis, stability, and/or transport from the VTA to the NAc. A similar extinction training regimen failed to alter TH levels in the NAc or VTA of rats trained to self-administer sucrose pellets, indicating that TH regulation in cocaine-trained animals is not a generalized effect of extinction learning per se. Rather, these data suggest that neuroadaptative responses during cocaine withdrawal ultimately are determined by a complex interaction between chronic drug exposure and drug-seeking experience. The ability of extinction training to restore NAc TH levels is hypothesized to accelerate recovery from dopamine depletion and anhedonia during cocaine withdrawal.

UR - http://www.scopus.com/inward/record.url?scp=0035320507&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035320507&partnerID=8YFLogxK

M3 - Article

C2 - 11264329

AN - SCOPUS:0035320507

VL - 21

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 7

ER -