This project will evaluate the role of the 5-HT2CR:5-HT2AR balance in impulsive action and cue reactivity in cocaine-dependent subjects as compared to non-drug using controls.
Name: Mirtazapine 15 MG (administered at Scan 1) and Placebo oral capsule (administered at Scan 2)
Description: 15mg of mirtazapine prior to scanType: DrugMirtazapine at Scan 1
Name: Placebo oral capsule (administered at Scan 1) and Mirtazapine 15 MG (administered at Scan 2)
Description: Oral placebo consisting of dextrose in gelatin capsuleType: DrugPlacebo at Scan 1
Description: fMRI activation during Go/NoGo (impulsivity) task with placebo dose vs Mirtazapine dose
Measure: Interaction of the serotonin receptor (5-HTR) type-2C Cys23Ser single nucleotide polymorphism (SNP) and a 5-HT2AR antagonist on the functional circuitry underlying impulsive action. Time: 1 dayDescription: fMRI activation during Attentional bias task with placebo dose vs Mirtazapine dose
Measure: Interaction of the 5-HT2CR Cys23Ser SNP and a 5-HT2AR antagonist on the functional circuitry underlying cue reactivity Time: 1 dayDescription: Impulsivity as measured by Go/NoGo task with placebo dose vs Mirtazapine dose
Measure: Effective connectivity involved in the 5-HT2AR:5-HT2CR homeostasis impulsive action Time: 1 dayDescription: Cue reactivity as measured by Attentional bias task with placebo dose vs Mirtazapine dose
Measure: Effective connectivity involved in the 5-HT2AR:5-HT2CR homeostasis cue reactivity Time: 1 dayDescription: fMRI activation with other 5-HT2CR SNPs during Attentional bias task with placebo dose vs Mirtazapine dose
Measure: Explore interactions between other 5-HT2CR SNPs and brain activation during attentional bias task after a 5- HT2AR antagonist Time: 1 dayDescription: fMRI activation with other 5-HT2CR SNPs during Go/NoGo (impulsivity) task with placebo dose vs Mirtazapine dose
Measure: Explore interactions between other 5-HT2CR SNPs and brain activation during Go/NoGo (impulsivity) task after a 5- HT2AR antagonist Time: 1 dayAllocation: Randomized
Crossover Assignment
There is one SNP
Interaction of the serotonin receptor (5-HTR) type-2C Cys23Ser single nucleotide polymorphism (SNP) and a 5-HT2AR antagonist on the functional circuitry underlying impulsive action.. fMRI activation during Go/NoGo (impulsivity) task with placebo dose vs Mirtazapine dose. --- Cys23Ser ---
Interaction of the 5-HT2CR Cys23Ser SNP and a 5-HT2AR antagonist on the functional circuitry underlying cue reactivity. --- Cys23Ser ---
Brain and behavioral responses to the 5-HT2AR blocking medication mirtazapine will be compared between subjects who have high and low functioning of the 5-HT2CR based on presence of a specific, functionally-relevant single nucleotide polymorphism (SNP) of the 5-HT2CR (Cys23Ser). --- Cys23Ser ---
The 5-HT2CR Cys23Ser SNP is thought to decrease the function of the protein and a preliminary observation indicates cocaine-dependent subjects carrying the CC genotype (Ser23 protein variant) display significantly higher cue reactivity. --- Cys23Ser ---