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 language | English (US) |
---|---|
Pages (from-to) | 827-833 |
Number of pages | 7 |
Journal | International Journal of Neuropsychopharmacology |
Volume | 10 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2007 |
Keywords
- Antidepressant
- Atipamezole
- Autoreceptor
- Desipramine
- Norepinephrine
ASJC Scopus subject areas
- General Medicine