Regulatory effects of reboxetine treatment alone, or following paroxetine treatment, on brain noradrenergic and serotonergic systems

Georgianna G. Gould, Marie Christine Pardon, David A. Morilak, Alan Frazer

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29 Scopus citations

Abstract

When patients do not respond to an initial antidepressant, one clinical approach is to switch to an agent in a different pharmacological class. However, few studies have examined the neurochemical consequences of this practice. To study this, we examined changes in binding sites in rat brain for norepinephrine (NET) and serotonin transporters (SERT), α1, α2, and β1 adrenergic receptors after chronic administration of paroxetine (PRX), reboxetine (RBX), or PRX followed by RBX. We also examined the effects of these treatments on mRNA expression for tyrosine hydroxylase (TH). RBX treatment for 3 weeks reduced NET binding significantly, by ∼40% in terminal field areas, and 6 weeks of RBX reduced it even more, by ∼60%. RBX treatment for 3 and 6 weeks reduced β1 adrenergic receptor-binding sites equally, by 50-60%. At no time did RBX treatment reduce SERT-binding sites. PRX treatment had no effect on β1 adrenergic or NET-binding sites, but reduced SERT-binding sites by 75-80%. Neither treatment altered mRNA for TH, α1, or α2 adrenergic receptor-binding sites. When 3 weeks of RBX treatment followed 3 weeks of PRX treatment, NET-binding sites were reduced to the same extent as measured after 6 weeks of RBX treatment alone, indicating that PRX pretreatment may have 'primed' the subsequent regulatory effect of RBX on the NET. Thus, pretreatment of rats with PRX actually enhanced at least one regulatory effect of RBX treatment on the noradrenergic system, and did not interfere with any other pharmacological effect caused by RBX treatment.

Original languageEnglish (US)
Pages (from-to)1633-1641
Number of pages9
JournalNeuropsychopharmacology
Volume28
Issue number9
DOIs
StatePublished - Sep 1 2003

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Keywords

  • Antidepressants
  • Norepinephrine transporter
  • Paroxetine
  • Quantitative autoradiography
  • Reboxetine
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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