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Author Notes:

Correspondence: Scott E. Hemby, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, One Biotech Place, 575 N. Patterson Avenue, Winston-Salem, NC 27157, USA e-mail: shemby@wakehealth.edu

Leonard Howell and Scott E. Hemby designed the experiments.

Scot McIntosh and Scott E. Hemby performed the experiments, collected and analyzed the data; Scott E. Hemby wrote the manuscript and Scot McIntosh and Leonard Howell provided critical review and suggestions.

Edited by: Alain Dervaux, Centre Hospitalier Sainte-Anne, France

Reviewed by: Hitoshi Morikawa, University of Texas at Austin, USA; Mark S. Brodie, University of Illinois at Chicago, USA

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Research Funding:

This work was supported by National Institutes of Health grants P50 DA006634 (Scott E. Hemby), DA027512 (Scott E. Hemby), and DA 010344(Leonard Howell) DA 000517 (Leonard Howell), RR000165 (Leonard Howell).

The authors have no competing financial interests.


  • anterior cingulate cortex
  • cocaine
  • dopamine
  • dorsolateral prefrontal cortex
  • orbitofrontal cortex
  • rhesus monkey

Dopaminergic dysregulation in prefrontal cortex of rhesus monkeys following cocaine self-administration


Journal Title:

Frontiers in Psychiatry


Volume 4, Number AUG


, Pages 88-88

Type of Work:

Article | Final Publisher PDF


Chronic cocaine administration regulates the expression of several proteins related to dopaminergic signaling and synaptic function in the mesocorticolimbic pathway, including the prefrontal cortex. Functional abnormalities in the prefrontal cortex are hypothesized to be due in part to the expression of proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys self-administered cocaine (i.v.) under limited (n = 4) and extended access conditions (n = 6). The abundance of surrogate markers of dopamine signaling and plasticity in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) were examined: glycosylated and non-glycosylated forms of the dopamine transporter (efficiency of dopamine transport), tyrosine hydroxylase (TH; marker of dopamine synthesis) and phosphorylated TH at Serine 30 and 40 (markers of enzyme activity), extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK 2), and phosphorylated ERK1 and ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity), and markers of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in dopamine signaling and response to cocaine). Extended cocaine access increased non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in TH expression were observed between groups for any of the regions, extended access induced significant elevations in pTHSer31 in all regions. In addition, a slight but significant reduction in phosphorylated pTHSer40 was found in the DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC but not in DLPFC or ACC. Furthermore, extended cocaine self-administration elicited significant increases in spinophilin protein expression in all regions. Results from the study provide insight into the biochemical alterations occurring in primate prefrontal cortex.

Copyright information:

© 2013 McIntosh, Howell and Hemby.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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