Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence

Effects of Corticorelin Administration on Dopamine Transmission, Craving, and Mood in Cocaine Dependence: A [11C]-(+)-PHNO PET Investigation

This study will, in a sample of cocaine-dependent and healthy control subjects, administer corticorelin and compare dopamine release between groups. Dopamine release will be measured using PET neuroimaging with the radiotracer [11C]-(+)-PHNO.

SCIENTIFIC SUMMARY The project will, in a sample of cocaine-dependent (CD) and healthy control (HC) subjects, use administration of Corticorelin, a synthetic form of corticotropin releasing factor (CRF)and PET imaging to assess dopamine (DA) transmission in addiction. We will use [11C]-(+)-PHNO PET to measure striatal DA receptor binding on two occasions: 1) following corticorelin administration and 2) following saline. The change in receptor binding between the two occasions (i.e., displacement of [11C]-(+)-PHNO by endogenous DA) will index DA release.

SUBJECTS CD subjects will meet DSM-IV criteria for abuse or dependence and be ~10d cocaine abstinent at the time of PET. HC will be recruited to match CD on age, sex, education, and cigarette smoking.

PRIMARY OUTCOME MEASURES We will measure [11C]-(+)-PHNO binding on two occasions (corticorelin, saline), with the difference between conditions indexing dopamine release; this measure will then be compared between cocaine-dependent and control subjects. We will also measure plasma cortisol and ACTH), physiological measures, and subjective craving and mood.

Inclusion Criteria:

• Sign and date informed consent
• Willing and able to complete trial as described in the protocol
• Psychiatrically healthy (as per diagnostic interview) except for cocaine dependence in cocaine users and nicotine dependence in both groups
• Mentally healthy
• Medically healthy (as per medical exam) with no current use of medications that may interfere with hormone activity or psychological measurements

Exclusion Criteria:

• Axis I psychiatric disorder (as per diagnostic interview), or medical condition that might interfere with participation in the study (as per medical exam)
• Exposure to radiation in the last 12 months exceeding the amount permissible by the CAMH PET centre
• Have received synthetic glucocorticoid or exogenous steroid therapy within one month of testing
• Exceed normal body weight
• If female: pregnancy or breast-feeding
• Metal implants or paramagnetic objects contained within the body
• Claustrophobia