Blockade of autoreceptor-mediated inhibition of norepinephrine release by atipamezole is maintained after chronic reuptake inhibition

M. Danet Lapiz, Zaorui Zhao, Corina O. Bondi, James M. O'Donnell, David A. Morilak

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The role of α2-adrenergic autoreceptor desensitization in the delayed onset of antidepressant efficacy of selective norepinephrine (NE) reuptake inhibitors is unclear. Using the α2-antagonist yohimbine, we showed previously that chronic treatment with desipramine (DMI) did not alter autoreceptor-mediated inhibition of NE release in the cortex. However, yohimbine may have non-selective effects that could confound this interpretation. Thus, using microdialysis, we measured acute effects of the highly selective α2-antagonist atipamezole on NE release in the prefrontal cortex following chronic DMI treatment, after 0-8 d washout. Atipamezole induced a similar elevation of extracellular NE in all treatment groups, indicating no change in autoreceptor function. Further, the effect was most rapid in DMI-treated rats with 0- and 2-d washout, suggesting that autoreceptor-mediated inhibition was most prominent when NE levels were highest. This provides further evidence that autoreceptor-mediated inhibition of NE neurotransmission remains functional after chronic DMI treatment, arguing against the hypothesis that desensitization of α2-autoreceptors accounts for the delayed onset of action of selective NE reuptake inhibitors.

Original languageEnglish (US)
Pages (from-to)827-833
Number of pages7
JournalInternational Journal of Neuropsychopharmacology
Volume10
Issue number6
DOIs
StatePublished - Dec 2007

Keywords

  • Antidepressant
  • Atipamezole
  • Autoreceptor
  • Desipramine
  • Norepinephrine

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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