Altered prefrontal dopaminergic function in chronic recreational ketamine users.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • December 2005

Published In

Volume / Issue

  • 162 / 12

Start / End Page

  • 2352 - 2359

PubMed ID

  • 16330601

Pubmed Central ID

  • 16330601

International Standard Serial Number (ISSN)

  • 0002-953X

Digital Object Identifier (DOI)

  • 10.1176/appi.ajp.162.12.2352

Language

  • eng

Conference Location

  • United States