[C-11]NPA PET-amphetamine in Cocaine Use Disorders
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- STATUS
- Recruiting
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- End date
- Sep 1, 2028
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- participants needed
- 30
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- sponsor
- Rajesh Narendran
Summary
This study uses [11C]NPA positron emission tomography (PET) and a d-amphetamine challenge to image amphetamine induced dopamine release in the striatum in subjects with cocaine use disorders (CUD). Amphetamine-induced dopamine release data from this study will be correlated with [11C]NOP-1A VT measured at baseline in the midbrain. [11C]NOP-1A PET data will be used from aim 1 (see, Study Record: Imaging CRF X NOP interactions in Cocaine Use Disorders)
Description
Cocaine use disorder (CUD) is a chronic disorder associated with numerous relapses and periods of abstinence.
Studies in CUD suggest that ~ 60 to 75% of abstinent addicts relapse over twelve months. Documenting specific neurochemical abnormalities that lead to relapse in individuals with CUD has the potential to accelerate the development of medications to prevent relapse. Basic investigations postulate an imbalance between brain stress and anti-stress/resilience systems as the underlying mechanism that drives negative reinforcement, craving, and relapse in addiction.. Nociceptin (N/OFQ), which binds to the nociceptive opioid peptide receptors (NOP) is a critical component of the brain's anti-stress system. N/OFQ exerts its anti-stress effect by counteracting the functional effects of the primary stress-promoting neuropeptide corticotrophin releasing factor (CRF) in the brain. Studies have also shown that acute increases in CRF and stress are countered by increased NOP receptor expression (~ 10% ) in brain regions that regulate stress such as bed nucleus of the stria terminalis. PET studies with the NOP radiotracer [11C]NOP-1A show increased binding to NOP in CUD compared to HC. PET studies also show NOP receptors to upregulate (~ 15%) in response to an acute intravenous hydrocortisone challenge (1 mg/Kg). NOP upregulation may represent an adaptive mechanism in the brain to counteract stress-induced increases in cortisol and CRF. Here, we postulate a failure in this adaptive mechanism as a reason that leads to relapse in CUD. CUD subjects and HC will be studied with [11C]NOP-1A before and after an intravenous hydrocortisone challenge (aim 1). Hydrocortisone is used as a challenge because it increases cortisol and CRF in brain regions that regulate stress. We hypothesize that hydrocortisone-induced increases in [11C]NOP-1A binding (DELTA VT) will be smaller in CUD relative to HC, and this will be associated with less time to relapse in a 12-week follow up. Mechanistic studies have also shown N/OFQ to act on ventral tegmental area/midbrain NOP receptors to inhibit the firing of dopamine neurons and limit reward to cocaine. Imaging amphetamine-induced dopamine release in a subset of CUD subjects who participate in aim 1 will allow us to link midbrain NOP receptor expression with ventral striatum (VST) dopamine release and examine its role in reinforcement (aim 2). The aims proposed in this study have the potential to clarify the role of N/OFQ and NOP in stress, reward, and relapse in CUD.
Details
| Condition | Cocaine Use Disorder |
|---|---|
| Treatment | d-amphetamine, Baseline [C-11]NPA PET Scan, Post-amphetamine [C-11]NPA PET Scan |
| Clinical Study Identifier | NCT05011760 |
| Sponsor | Rajesh Narendran |
| Last Modified on | 12 September 2021 |
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