Abstract
Background
A deficiency of mesolimbic dopamine (DA) is a leading candidate for the etiology of
certain symptoms of depression (e.g., anhedonia and loss of motivation). Here we show
amounts of dopaminergic proteins in the amygdala, a key brain structure involved in
the integration of emotions and stress, in subjects with major depression and in psychiatrically
normal control subjects.
Methods
The specific binding of [125I]RTI 55 to the DA transporter, [3H]SCH 23390 to the D1 receptor and [125I]epidepride to D2/D3 receptors were measured in the right amygdaloid complex in postmortem
brains from 11 subjects with major depression and 11 matched control subjects.
Results
The binding of [125I]RTI 55 to DA transporter was significantly lower in the basal and central amygdaloid
nuclei, whereas the binding of [125I]epidepride to D2/D3 receptors was significantly higher in the basal, central, and
lateral amygdaloid nuclei in major depression compared with control subjects. No difference
in the binding of [3H]SCH 23390 to D1 receptors was observed.
Conclusions
Given that DA depletion in rats can induce a reduction in the DA transporter and an
upregulation of D2/D3 receptors, our data are consistent with the hypothesis that
major depression is associated with a deficiency of mesolimbic DA.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Metabolic rate in the right amygdala predicts negative affect in depressed patients.Neuroreport. 1998; 9: 3301-3307
- The contribution of the amygdala to normal and abnormal emotional states.Trends Neurosci. 1993; 16: 328-333
American Psychiatric Association (1987): Diagnostic and Statistical Manual of Mental Disorders, Third Edition. Washington, DC.
- The family history method using diagnostic criteria. Reliability and validity.Arch Gen Psychiatry. 1977; 34: 1229-1235
- Quantitative histochemistry of acetylcholinesterase in rat and human brain postmortem.J Neurosci Methods. 1986; 16: 39-45
- Monoamine dysfunction and the pathophysiology and treatment of depression.J Clin Psychiatry. 1998; 59: 11-14
- D1 and D2 dopamine binding site up-regulation and apomorphine-induced stereotypy.Pharmacol Biochem Behav. 1987; 28: 477-482
- Immunocytochemical localization of the dopamine transporter in human brain.J Comp Neurol. 1999; 409: 38-56
- The dopamine transporter.J Neurosci. 1995; 15: 1714-1723
- Localization and quantification of the dopamine transporter.Brain Res. 1995; 690: 217-224
- Nigrostriatal lesions enhance striatal 3H-apomorphine and 3H-spiroperidol binding.Eur J Pharmacol. 1979; 56: 277-281
- Sleep deprivation increases dopamine D1 receptor antagonist [3H]SCH 23390 binding and dopamine-stimulated adenylate cyclase in the rat limbic system.Neurosci Lett. 1990; 117: 224-227
- Dopamine D2 receptors in depression measured with single photon emission computed tomography.Biol Psychiatry. 1994; 35: 128-132
- Neuroimaging studies in mood disorders.Biol Psychiatry. 2000; 48: 801-812
- Neuroanatomical circuits in depression.Psychopharmacol Bull. 1992; 28: 261-274
- A functional anatomical study of unipolar depression.J Neurosci. 1992; 12: 3628-3641
- Dopamine and depression–striatal dopamine D2 receptor SPECT before and after antidepressant therapy.Psychopharmacology (Berl). 1996; 126: 91-94
- Neural degeneration and the transport of neurotransmitters.Ann Neurol. 1993; 34: 638-645
- A diagnostic interview.Arch Gen Psychiatry. 1978; 35: 837-844
- Distribution of monoamines within the amygdala.in: Aggleton J.P. The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. Wiley-Liss, New York1992: 97-114
- Modulatory effect of agents active in the presynaptic dopaminergic system on the striatal dopamine transporter.Eur J Pharmacol. 1996; 298: 27-30
- Distribution of dopamine D3 receptor expressing neurons in the human forebrain.Neuropsychopharmacology. 1999; 20: 60-80
- Antidepressant drugs affect dopamine uptake.Biochem Pharmacol. 1975; 24: 1896-1897
- Dopamine D(3) receptor as a therapeutic target for antipsychotic and antiparkinsonian drugs.Pharmacol Ther. 2001; 90: 231-259
- Characterization and distribution of [125I] epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain.J Pharmacol Exp Ther. 1991; 257: 1253-1263
- Distribution of D1- and D2-like dopamine receptors in human brain.in: Niznik H.B. Dopamine Receptors and Transporters; Pharmacology, Structure and Function. Marcel Dekker, New York1994: 345-382
- Repeated administration of antidepressants enhances agonist affinity for mesolimbic D2-receptors.J Pharm Pharmacol. 1989; 41: 555-558
- Reduced levels of norepinephrine transporters in the locus coeruleus in major depression.J Neurosci. 1997; 17: 8451-8458
- Recent biochemical studies of the dopamine transporter.Life Sci. 1998; 62: 1573-1575
- Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness.Arch Gen Psychiatry. 2000; 57: 787-793
- Characterization and localization of [125I]RTI-121 binding sites in human striatum and medial temporal lobe.J Pharmacol Exp Ther. 1995; 274: 1473-1483
- Cocaine use increases [3H]WIN 35428 binding sites in human striatum.Brain Res. 1993; 628: 17-25
- Cell-type-specific expression of catecholamine transporters in the rat brain.J Neurosci. 1994; 14: 4903-4914
- Repeated treatment with antidepressant drugs potentiates the locomotor response to (+)-amphetamine.J Pharm Pharmacol. 1984; 36: 127-130
- Repeated treatment with antidepressant drugs increases the behavioural response to apomorphine.J Neural Transm. 1984; 60: 273-282
- Desipramine given repeatedly enhances behavioural effects of dopamine and D-amphetamine injected into the nucleus accumbens.Eur J Pharmacol. 1987; 140: 179-185
- Effects of clorgyline and pargyline on deaminated metabolites of norepinephrine, dopamine and serotonin in human cerebrospinal fluid.J Neurochem. 1979; 32: 229-231
- Decreased striatal D1 binding density following mesotelencephalic 6-hydroxydopamine injections.Brain Res. 1989; 493: 247-257
- Limbic-cortical dysregulation.J Neuropsychiatry Clin Neurosci. 1997; 9: 471-481
- Repeated reserpine administration up-regulates the transduction mechanisms of D1 receptors without changing the density of [3H]SCH 23390 binding.Brain Res. 1989; 483: 117-122
- Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain.Proc Natl Acad Sci USA. 1994; 91: 11271-11275
- Sodium-dependent isomerization of dopamine D-2 receptors characterized using [125I]epidepride, a high-affinity substituted benzamide ligand.J Pharmacol Exp Ther. 1990; 252: 1108-1116
- The dopamine transporter.J Neurosci. 1997; 17: 6899-6907
- The dopamine transporter is localized to dendritic and axonal plasma membranes of nigrostriatal dopaminergic neurons.J Neurosci. 1996; 16: 436-447
- Differential recovery rates of rat D2 dopamine receptors as a function of aging and chronic reserpine treatment following irreversible modification.J Neurosci. 1987; 7: 1484-1491
- Pharmacology and distribution of norepinephrine transporters in the human locus coeruleus and raphe nuclei.J Neurosci. 1997; 17: 1710-1719
- Parallel changes in dopamine D2 receptor binding in limbic forebrain associated with chronic mild stress-induced anhedonia and its reversal by imipramine.Psychopharmacology (Berl). 1994; 115: 441-446
- Mania, depression and brain dopamine.in: Essman W.B. Valzelli L. Current Developments in Psychopharmacology. Spectrum, New York1975: 206-248
- Dopamine transporter immunohistochemistry in median eminence, amygdala, and other areas of the rat brain.Synaps. 1996; 22: 93-99
- NIMH Diagnostic Interview Schedule. Version III—Revised (DIS-III-R). Washington University Department of Psychiatry, St. Louis, MO1989
- Acute in vivo amphetamine produces a homologous desensitization of dopamine receptor-coupled adenylate cyclase activities and decreases agonist binding to the D1 site.Mol Pharmacol. 1989; 35: 139-147
- Dopamine D3 receptor is decreased and D2 receptor is elevated in the striatum of Parkinson’s disease.Mov Disord. 1998; 13: 788-797
- Clinical and psychometric correlates of dopamine D2 binding in depression.Psychol Med. 1997; 27: 1247-1256
- The effect of chronic treatment with a novel aryl-piperazine antipsychotic on monoamine receptors in rat brain.Brain Res. 1995; 677: 250-256
- Amygdala core nuclei volumes are decreased in recurrent major depression.Neuroreport. 1998; 9: 2023-2028
- Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.Arch Gen Psychiatry. 1997; 54: 233-241
- The human amygdaloid complex.Neuroscience. 1990; 36: 449-472
- D1 dopamine receptor binding in mood disorders measured by positron emission tomography.Psychopharmacology (Berl). 1992; 106: 14-18
- Dopamine, schizophrenia, mania, and depression.Behav Brain Sci. 1987; 10: 197-245
- Reserpine-induced up-regulation of dopamine D2 receptors in the rat striatum is enhanced by denervation but not by chronic receptor blockade.Neurosci Lett. 1986; 70: 245-249
- Effect of reserpine on the monoamine oxidase (MAO) activity in rat liver and brain.Biochem Pharmacol. 1978; 27: 1985-1986
- Behavioral depression produced by an uncontrollable stressor.Brain Res Rev. 1981; 3: 167-205
- Dopamine and depression.Brain Res. 1983; 287: 225-236
- Dopamine and depression.Brain Res. 1983; 287: 237-246
- Dopaminergic mechanisms in depression and mania.in: Bloom F.E. Kupfer D.J. Psychopharmacology: The Fourth Generation of Progress. Raven Press, New York1995: 921-931
- Dopamine transporter changes in neuropsychiatric disorders.Adv Pharmacol. 1998; 42: 219-223
- Expression and regulation of the human dopamine transporter in a neuronal cell line.Brain Res Mol Brain Res. 1998; 59: 66-73
Article info
Publication history
Accepted:
February 12,
2002
Received in revised form:
February 7,
2002
Received:
September 10,
2001
Identification
Copyright
© 2002 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
