QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 4, 2009, 29(9):2876-2884; doi:10.1523/JNEUROSCI.5638-08.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Shen, H.-w. Articles by Kalivas, P. W. Search for Related Content PubMed PubMed Citation Articles by Shen, H.-w. Articles by Kalivas, P. W.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Altered Dendritic Spine Plasticity in Cocaine-Withdrawn Rats

Hao-wei Shen,^1 * Shigenobu Toda,^1 * Khaled Moussawi,¹ Ashley Bouknight,¹ Daniel S. Zahm,² and Peter W. Kalivas¹

¹Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, and ²Department of Pharmacology and Physiological Sciences, Saint Louis University School of Medicine, St. Louis, Missouri 63104

Correspondence should be addressed to Shigenobu Toda at his present address: Department of Psychiatry, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan. Email: todas{at}med.kanazawa-u.ac.jp

Chronic cocaine treatment is associated with changes in dendritic spines in the nucleus accumbens, but it is unknown whether this neuroplasticity alters the effect of a subsequent cocaine injection on spine morphology and protein content. Three weeks after daily cocaine or saline administration, neurons in the accumbens were filled with the lipophilic dye, DiI. Although daily cocaine pretreatment did not alter spine density compared with daily saline, there was a shift from smaller to larger diameter spines. During the first 2 h after an acute cocaine challenge, a bidirectional change in spine head diameter and increase in spine density was measured in daily cocaine-pretreated animals. In contrast, no change in spine diameter or density was elicited by a cocaine challenge in daily saline animals during the first 2 h after injection. However, spine density was elevated at 6 h after a cocaine challenge in daily saline-pretreated animals. The time-dependent profile of proteins in the postsynaptic density subfraction elicited by a cocaine challenge in daily cocaine-pretreated subjects indicated that the changes in spine diameter and density were associated with a deteriorating actin cytoskeleton and a reduction in glutamate signaling-related proteins. Correspondingly, the amplitude of field potentials in accumbens evoked by stimulating prefrontal cortex was reduced for up to 6 h after acute cocaine in daily cocaine-withdrawn animals. These data indicate that daily cocaine pretreatment dysregulates dendritic spine plasticity elicited by a subsequent cocaine injection.

---

Received Nov. 25, 2008; revised Feb. 1, 2009; accepted Feb. 1, 2009.

Correspondence should be addressed to Shigenobu Toda at his present address: Department of Psychiatry, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641, Japan. Email: todas{at}med.kanazawa-u.ac.jp

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help