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

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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)
Pages (from-to)RC137
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume21
Issue number7
StatePublished - Apr 1 2001

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ASJC Scopus subject areas

  • Neuroscience(all)

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