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Kappa-opioid receptors, dynorphin, and cocaine addiction: a positron emission tomography study
- Source :
- Neuropsychopharmacology
- Publication Year :
- 2018
-
Abstract
- Animal studies indicate that the kappa-opioid receptor/dynorphin system plays an important role in cocaine binges and stress-induced relapse. Our goal was to investigate changes in kappa-opioid receptor (KOR) availability in the human brain using positron emission tomography (PET), before and after a cocaine binge. We also investigated the correlation between KOR and stress-induced cocaine self-administration. PET imaging was performed with the KOR selective agonist [(11)C]GR103545. Subjects with cocaine-use disorder (CUD) underwent PET scans and performed two types of cocaine self-administration sessions in the laboratory as follows: (1) choice sessions following a cold pressor test, to induce stress, and (2) binge dosing of cocaine. This allowed us investigate the following: (1) the association between KOR binding and a laboratory model of stress-induced relapse and (2) the change in KOR binding following a 3-day cocaine binge, which is thought to represent a change in endogenous dynorphin. A group of matched healthy controls was included to investigate between group differences in KOR availability. A significant association between [(11)C]GR103545 binding and cocaine self-administration was seen: greater KOR availability was associated with more choices for cocaine. In addition, the 3-day cocaine binge significantly reduced [(11)C]GR103545 binding by 18% in the striatum and 14% across brain regions. No difference in [(11)C]GR103545 binding was found between the CUD subjects and matched controls. In the context of previous studies, these findings add to the growing evidence that pharmacotherapies targeting the KOR have the potential to significantly impact treatment development for cocaine-use disorder.
- Subjects :
- Agonist
Adult
Male
medicine.medical_specialty
Pyrrolidines
medicine.drug_class
media_common.quotation_subject
Narcotic Antagonists
Context (language use)
Striatum
Dynorphin
κ-opioid receptor
Choice Behavior
Dynorphins
Cocaine Smoking
Piperazines
Article
03 medical and health sciences
Cocaine-Related Disorders
0302 clinical medicine
Cocaine
Internal medicine
medicine
Humans
Carbon Radioisotopes
media_common
Pharmacology
business.industry
Addiction
Receptors, Opioid, kappa
Cold pressor test
Brain
Human brain
Middle Aged
Naltrexone
030227 psychiatry
Neostriatum
Psychiatry and Mental health
Endocrinology
medicine.anatomical_structure
Case-Control Studies
Positron-Emission Tomography
business
030217 neurology & neurosurgery
Stress, Psychological
Subjects
Details
- ISSN :
- 1740634X
- Volume :
- 44
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
- Accession number :
- edsair.doi.dedup.....478f31170e78fef334a5bc08224c0bee