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

Citation
Ef. Schmidt et al., Extinction training regulates tyrosine hydroxylase during withdrawal from cocaine self-administration, J NEUROSC, 21(7), 2001, pp. NIL_5
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
7
Year of publication
2001
Database
ISI
SICI code
0270-6474(20010401)21:7<NIL_5:ETRTHD>2.0.ZU;2-4
Abstract
Chronic exposure to drugs of abuse is known to modulate tyrosine hydroxylas e (TH) levels in the mesolimbic dopamine system. In this study, 12 d of coc aine 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 withdr awal period. In contrast, TH immunoreactivity in the NAc was completely res tored in animals that experienced extinction training (4 hr/d) during the s ame 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 a lter 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 sugge st 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 le vels is hypothesized to accelerate recovery from dopamine depletion and anh edonia during cocaine withdrawal.