2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane and Anhedonia

Although the involvement of dopamine in gambling disorder (GD) has long been hypothesized, its precise role remains unclear. The action of dopamine in the synapses is regulated by the dopamine transporter (DAT). We hereinafter present significant differences between a sample of 15 treatment-seeking GD subjects and 17 healthy controls in terms of striatal DAT availability, and we explore its association with reward-based decision making. We performed

Topics: Adolescent; Adult; Aged; Anhedonia; Corpus Striatum; Decision Making; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Gambling; Humans; Impulsive Behavior; Male; Middle Aged; Psychometrics; Radiopharmaceuticals; Reward; Signal Transduction; Synapses; Tomography, Emission-Computed, Single-Photon; Tropanes; Young Adult

Extended-release naltrexone (XRNT), an opioid receptor antagonist, is successfully used in the treatment of opioid dependence. However, naltrexone treatment of opioid-dependent patients may reduce striatal dopamine transporter (DAT) availability and cause depression and anhedonia.. The aim of this study is to investigate changes in striatal DAT availability and symptoms of depression (Beck Depression Inventory (BDI)) and anhedonia (Snaith Hamilton Pleasure Scale (SHAPS)) before and during XRNT treatment.. At baseline, ten detoxified heroin-dependent patients and 11 matched healthy controls underwent [(123)I]FP-CIT single photon emission computed tomography (SPECT) imaging to assess striatal DAT binding. Patients underwent a second SPECT scan 2 weeks after an intramuscular injection with XRNT.. At baseline, the mean binding potential (BPND) in the putamen was at a trend level lower and the mean BDI score was significantly higher in heroin patients (n = 10) than in controls (n = 11) (3.45 ± 0.88 vs. 3.80 ± 0.61, p = 0.067, d = -0.48 and 12.75 ± 7.40 vs. 5.20 ± 4.83, p = 0.019, d = 1.24, respectively). Post hoc analyses in subgroups with negative urine analyses for opioids and cocaine showed significantly lower baseline putamen BPND in heroin patients (n = 8) than controls (n = 10) (3.19 ± 0.43 vs. 3.80 ± 0.64, p = 0.049, d = -1.03). XRNT treatment in heroin patients was not significantly associated with changes in striatal DAT availability (p = 0.348, d = 0.48), but the mean BDI score after XRNT treatment was significantly lower than before treatment (7.75 ± 7.21 vs. 12.75 ± 7.40, p = 0.004, d = -0.68).. The results of this study suggest that XRNT treatment does not reduce striatal DAT availability and has no significant effect on anhedonia, but is associated with a significant reduction of depressive symptoms.

Topics: Adult; Anhedonia; Corpus Striatum; Delayed-Action Preparations; Depression; Diagnostic and Statistical Manual of Mental Disorders; Dopamine Plasma Membrane Transport Proteins; Female; Heroin Dependence; Humans; Male; Middle Aged; Naltrexone; Narcotic Antagonists; Neuropsychological Tests; Positron-Emission Tomography; Psychiatric Status Rating Scales; Radiopharmaceuticals; Substance Abuse Detection; Tomography, Emission-Computed, Single-Photon; Tropanes

Dopamine is an important neurotransmitter involved in the pathophysiology of depression and anhedonia. Dopamine transporters (DAT) may play a crucial role in the pathophysiology of dopaminergic transmission. We investigated the relationship between striatal DAT availability and depression, pointing out possible correlations with anhedonia and treatment outcomes.. Ten depressed patients with anhedonia, 10 depressed patients without anhedonia and 20 healthy controls underwent single photon emission computed tomography using (123)I-FP-CIT [(123)I-N-ω-fluoropropyl-carbomethoxy-3β-(4-iodophenyl)tropane]. Psychometric measures included the Snaith-Hamilton Pleasure Scale and the Hamilton Depression Rating Scale. A further assessment of DAT availability was performed in the 10 patients with marked anhedonia after a 3-month pharmacological treatment.. Depressed patients with and without anhedonia showed significantly lower (123)I-FP-CIT binding ratios in the bilateral striatum, caudate and putamen. No significant changes were detected after treatment in the 10 patients with marked anhedonia. When considering clinical outcomes, subjects with remission of depression showed a significant reduction of (123)I-FP-CIT binding ratios in all regions at baseline, but after treatment no differences were found any longer.. We suppose that a hypofunction of the striatal dopaminergic system may be a 'state' feature of a depressive condition as a whole rather than anhedonia itself. On the other hand, some anhedonic features mainly represent an enduring trait that persists independently of mood state.

Topics: Adult; Anhedonia; Corpus Striatum; Depressive Disorder; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Iodine Radioisotopes; Male; Middle Aged; Tomography, Emission-Computed, Single-Photon; Tropanes