Article

Lower dopamine transporter binding potential in striatum during depression

PET Imaging Centre, and Mood Division, Centre for Addiction and Mental Health, Department of Psychiatry and University of Toronto, 250 College St., Toronto, Ont. M5T1R8, Canada.
Neuroreport (Impact Factor: 1.64). 01/2002; 12(18):4121-5. DOI: 10.1097/00001756-200112210-00052
Source: PubMed

ABSTRACT Previous studies suggest that there is a dopamine lowering process during major depressive episodes (MDE). To investigate this, we measured the dopamine transporter binding potential (DAT BP) in the striatum of depressed and healthy subjects using [(11)C]RTI-32 PET. The DAT, a predominantly presynaptic receptor, decreases in density after chronic dopamine depletion and the BP is proportional to receptor density. In all striatal regions, subjects with MDE had significantly lower DAT BP. Low striatal DAT BP in MDE is consistent with a downregulation of DAT in response to a dopamine lowering process. There was also a strong, highly significant, inverse correlation between striatal DAT BP and neuropsychological tests of dopamine-implicated symptoms in patients (i.e. patients with lower DAT BP performed better). Lower DAT BP itself reduces extracellular clearance of dopamine. Patients who did not decrease their striatal DAT BP failed to compensate for low dopamine and showed greater impairment on dopamine related tests.

0 Followers
 · 
183 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We used animal models of "forced swim stress" and "chronic unpredictable stress", and tried to reveal whether a passive coping style of high flotation behavior in forced swim stress predicts anhedonia behavior after chronic unpredictable stress, and whether the dopamine system regulates floating and anhedonia behaviors. Our results confirmed that depression-prone rats use "floating behavior" as a coping strategy in forced swim stress and more readily suffer from anhedonia during chronic unpredictable stress. Intraperitoneal injection or nucleus accumbens microinjection of the dopamine 2/3 receptor subtype agonist ropinirole reduced floating behaviors in depression-prone animals, but increased sucrose preference in rats showing anhedonia. These data indicate that floating behavior is a defensive mode that is preferred by susceptible individuals under conditions of acute stress. Simultaneously, these animals more readily experienced anhedonia under long-term stress; that is, they were more readily affected by depression. Our results suggest that dopamine 2/3 receptor subtypes in the nucleus accumbens play an important role in floating behaviors and anhedonia.
    Neural Regeneration Research 08/2014; 9(15):1464-73. DOI:10.4103/1673-5374.139464 · 0.23 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Many studies have shown that chronic stress can cause neuronal damage and depression, but this exact mechanism still remains unknown. Neurons are vulnerable to lipid peroxidation-induced damage because the major part of neuronal cell membrane is polyunsaturated fatty acids that are substrate for reactive oxygen species. Since endogenous antioxidant defense systems normally eliminate production of reactive oxygen species, deficient antioxidant defense can cause oxidative stress-induced damage. In the present study, to understand the role of endogenous antioxidant defense in chronic stress-induced neuronal damage, we analyzed lipid peroxidation, total antioxidant capacity, and activities of catalase and glutathione peroxidase in frontal cortex, hippocampus and striatum of rats exposed to chronic unpredictable stress. We found that chronic unpredictable stress for four weeks in rats induced depressive-like behaviors such as anhedonia, despair and decreased exploration. Malondialdehyde, a lipid peroxidation product, is increased, but total antioxidant capacity, glutathione peroxidase activity and catalase activity are decreased in brain of rats exposed to chronic unpredictable stress. Our findings suggest that down regulation of endogenous antioxidant defense induces lipid peroxidation contributing a role to chronic stress and depression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Neuroscience Letters 10/2014; 584C:208-213. DOI:10.1016/j.neulet.2014.10.031 · 2.06 Impact Factor