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Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates.

Publication ,  Journal Article
Sizemore, GM; Co, C; Koves, TR; Martin, TJ; Smith, JE
Published in: Psychopharmacology (Berl)
February 2004

RATIONALE: Neurotoxin induced lesions of dopamine-releasing neurons that innervate the nucleus accumbens (NAcc) alter cocaine self-administration. In addition, elevated extracellular levels of NAcc dopamine (DA) are thought to be central to the biological mechanisms that underlie this behavior. OBJECTIVES: This study assessed the long-term effects of 6-hydroxydopamine (6-OHDA) induced lesions of the NAcc on cocaine self-administration and the dialysate levels of dopamine ([DA](d)) in this structure to determine if recovery of drug intake was correlated with the DA response. METHODS: Rats implanted with jugular catheters and bilateral cannulas were trained to self-administer cocaine and subsequently received bilateral intracranial micro-injections of 6-OHDA or vehicle into the NAcc. The levels of DA and cocaine were determined in microdialysates of the NAcc collected during experimental sessions 6-7, 14-16, 29-30, and 44-46 days post-treatment. RESULTS: The 6-OHDA induced lesions significantly reduced cocaine self-administration for 3 weeks while vehicle treatment had a moderate effect for the first several days. Cocaine-induced increases in NAcc [DA](d) did not return to sham/vehicle treated control levels for 6 weeks in the lesioned group and DA content in the NAcc was 46% of control at 44 days post-lesion. CONCLUSIONS: Although dopaminergic lesions of the NAcc produced profound effects on cocaine self-administration, responding recovered to control levels before cocaine-induced increases in NAcc [DA](d) while content of DA in the NAcc did not recover. These data suggest that the plasticity of neuronal systems in the NAcc related to cocaine self-administration and their response following 6-OHDA lesions is more complex than restoration of DAergic tone.

Duke Scholars

Published In

Psychopharmacology (Berl)

DOI

ISSN

0033-3158

Publication Date

February 2004

Volume

171

Issue

4

Start / End Page

413 / 420

Location

Germany

Related Subject Headings

  • Time Factors
  • Self Administration
  • Rats, Inbred F344
  • Rats
  • Psychiatry
  • Oxidopamine
  • Nucleus Accumbens
  • Microdialysis
  • Male
  • Dose-Response Relationship, Drug
 

Citation

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Sizemore, G. M., Co, C., Koves, T. R., Martin, T. J., & Smith, J. E. (2004). Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates. Psychopharmacology (Berl), 171(4), 413–420. https://doi.org/10.1007/s00213-003-1596-6
Sizemore, Glen M., Conchita Co, Timothy R. Koves, Thomas J. Martin, and James E. Smith. “Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates.Psychopharmacology (Berl) 171, no. 4 (February 2004): 413–20. https://doi.org/10.1007/s00213-003-1596-6.
Sizemore, Glen M., et al. “Time-dependent recovery from the effects of 6-hydroxydopamine lesions of the rat nucleus accumbens on cocaine self-administration and the levels of dopamine in microdialysates.Psychopharmacology (Berl), vol. 171, no. 4, Feb. 2004, pp. 413–20. Pubmed, doi:10.1007/s00213-003-1596-6.
Journal cover image

Published In

Psychopharmacology (Berl)

DOI

ISSN

0033-3158

Publication Date

February 2004

Volume

171

Issue

4

Start / End Page

413 / 420

Location

Germany

Related Subject Headings

  • Time Factors
  • Self Administration
  • Rats, Inbred F344
  • Rats
  • Psychiatry
  • Oxidopamine
  • Nucleus Accumbens
  • Microdialysis
  • Male
  • Dose-Response Relationship, Drug