Chronic hypercortisolemia inhibits dopamine synthesis and turnover in the nucleus accumbens: An in vivo microdialysis study

Karel Pacak, Olga Tjurmina, Miklós Palkovits, David S. Goldstein, Christian A. Koch, Thomas Hoff, George P. Chrousos

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Over 60% of patients with Cushing's syndrome suffer from major depression, which frequently abates after correction of the hypercortisolism. The mesolimbic and mesocortical dopaminergic (DAergic) systems are thought to participate in psychiatric disorders. In this study, we investigated whether hypercortisolemia affects indices of DAergic activity in the nucleus accumbens (NAc) and the prefrontal cortex (PFC) of freely moving rats. Cortisol (CORT, 25 mg/kg/day) was infused subcutaneously for 7 days via an osmotic minipump. Microdialysate collection (30-min periods, 2 μl/min) began 24 h after probe placement. Concentrations of dihydroxyphenylalanine (DOPA) in interstitial fluid in the nucleus accumbens (NAc) and perifrontal cortex (PFC) were measured before and after local perfusion with NSD-1015, an irreversible inhibitor of L-aromatic amino acid decarboxylase, to assess local dopamine (DA) biosynthesis. The sum of microdialysate DA, dihydroxyphenylacetic acid, and homovanillic acid was used as an index of local DA turnover. DOPA accumulation after NSD-1015 was markedly attenuated in CORT-treated compared with saline-treated animals (5,703 ± 1,849 vs. 10,902 ± 2,454 pg/ml; p < 0.01). In contrast, the two groups did not differ in DOPA accumulation in the PFC. Values for the turnover index of DA were also significantly lower in CORT-treated animals in the NAc but not in the PFC. The results indicate that CORT inhibits DA synthesis and turnover in the NAc but not in the PFC. Region-specific CORT-induced inhibition of DAergic activity may help to explain depressive symptoms in patients with chronic hypercortisolemia and normalization after medical or surgical correction of hypercortisolism.

Original languageEnglish
Pages (from-to)148-157
Number of pages10
JournalNeuroendocrinology
Volume76
Issue number3
DOIs
Publication statusPublished - 2002

Keywords

  • Adrenal steroids
  • Amino acid decarboxylase
  • Catecholamines
  • Dihydroxyphenylacetic acid
  • Dihydroxyphenylalanine
  • Homovanillic acid
  • Nucleus accumbens
  • Prefrontal cortex

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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