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Altered prefrontal dopaminergic function in chronic recreational ketamine users.

Publication ,  Journal Article
Narendran, R; Frankle, WG; Keefe, R; Gil, R; Martinez, D; Slifstein, M; Kegeles, LS; Talbot, PS; Huang, Y; Hwang, D-R; Khenissi, L; Cooper, TB ...
Published in: Am J Psychiatry
December 2005

OBJECTIVE: Ketamine is a noncompetitive antagonist at the glutamatergic N-methyl-D-aspartate (NMDA) receptor that is used in human and animal medicine as an injectable anesthetic. The illegal use of ketamine as a recreational drug is rapidly growing. Very little is currently known about the consequences of repeated ketamine exposure in the human brain. Animal studies indicate that the prefrontal dopaminergic system is particularly vulnerable to the toxic effects of repeated administration of NMDA antagonists. In this study, dopamine D1 receptor availability was assessed by using positron emission tomography and the selective D1 receptor radioligand [11C]NNC 112 in a group of 14 recreational chronic ketamine users and matched healthy subjects. METHOD: History of ketamine abuse was confirmed in subjects by hair analysis. [11C]NNC 112 binding potential was measured with kinetic analysis using the arterial input function. RESULTS: Dorsolateral prefrontal cortex D1 receptor availability was significantly up-regulated in chronic ketamine users ([11C]NNC 112 binding potential: mean=1.68 ml/g, SD=0.40) relative to comparison subjects (mean=1.35 ml/g, SD=0.35). No significant differences were noted in other cortical, limbic, or striatal regions. In the chronic ketamine user group, dorsolateral prefrontal cortex [11C]NNC 112 binding potential up-regulation was significantly correlated with the number of vials of ketamine (with a vial representing approximately 200-300 mg of ketamine) used per week. CONCLUSIONS: Chronic ketamine users exhibited a regionally selective up-regulation of D1 receptor availability in the dorsolateral prefrontal cortex, a phenomenon observed following chronic dopamine depletion in animal studies. These data suggest that the repeated use of ketamine for recreational purposes affects prefrontal dopaminergic transmission, a system critically involved in working memory and executive function.

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Published In

Am J Psychiatry

DOI

ISSN

0002-953X

Publication Date

December 2005

Volume

162

Issue

12

Start / End Page

2352 / 2359

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tissue Distribution
  • Substance-Related Disorders
  • Substance Abuse Detection
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Dopamine
  • Psychiatry
  • Prefrontal Cortex
  • Positron-Emission Tomography
  • Memory
 

Citation

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Narendran, R., Frankle, W. G., Keefe, R., Gil, R., Martinez, D., Slifstein, M., … Abi-Dargham, A. (2005). Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry, 162(12), 2352–2359. https://doi.org/10.1176/appi.ajp.162.12.2352
Narendran, Rajesh, W Gordon Frankle, Richard Keefe, Roberto Gil, Diana Martinez, Mark Slifstein, Lawrence S. Kegeles, et al. “Altered prefrontal dopaminergic function in chronic recreational ketamine users.Am J Psychiatry 162, no. 12 (December 2005): 2352–59. https://doi.org/10.1176/appi.ajp.162.12.2352.
Narendran R, Frankle WG, Keefe R, Gil R, Martinez D, Slifstein M, et al. Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry. 2005 Dec;162(12):2352–9.
Narendran, Rajesh, et al. “Altered prefrontal dopaminergic function in chronic recreational ketamine users.Am J Psychiatry, vol. 162, no. 12, Dec. 2005, pp. 2352–59. Pubmed, doi:10.1176/appi.ajp.162.12.2352.
Narendran R, Frankle WG, Keefe R, Gil R, Martinez D, Slifstein M, Kegeles LS, Talbot PS, Huang Y, Hwang D-R, Khenissi L, Cooper TB, Laruelle M, Abi-Dargham A. Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry. 2005 Dec;162(12):2352–2359.
Journal cover image

Published In

Am J Psychiatry

DOI

ISSN

0002-953X

Publication Date

December 2005

Volume

162

Issue

12

Start / End Page

2352 / 2359

Location

United States

Related Subject Headings

  • Up-Regulation
  • Tissue Distribution
  • Substance-Related Disorders
  • Substance Abuse Detection
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Dopamine
  • Psychiatry
  • Prefrontal Cortex
  • Positron-Emission Tomography
  • Memory