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Altered prefrontal dopaminergic function in chronic recreational ketamine users
- Source :
- The American journal of psychiatry. 162(12)
- Publication Year :
- 2005
-
Abstract
- 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.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.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.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.
- Subjects :
- Adult
Male
medicine.medical_specialty
Substance-Related Disorders
Dopamine
Prefrontal Cortex
Receptors, N-Methyl-D-Aspartate
Functional Laterality
Receptors, Dopamine
Dopamine receptor D1
Memory
Internal medicine
medicine
Radioligand
Humans
Ketamine
Tissue Distribution
Carbon Radioisotopes
Prefrontal cortex
Benzofurans
Analgesics
Illicit Drugs
Dopaminergic
Benzazepines
Up-Regulation
Dorsolateral prefrontal cortex
Substance Abuse Detection
Psychiatry and Mental health
medicine.anatomical_structure
Endocrinology
Positron-Emission Tomography
NMDA receptor
Female
Psychology
medicine.drug
Hair
Subjects
Details
- ISSN :
- 0002953X
- Volume :
- 162
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- The American journal of psychiatry
- Accession number :
- edsair.doi.dedup.....897c695ea4b91f7f1b17059be009a11d