Antidepressant-induced regulation of 5-HT(1b) mRNA in rat dorsal raphe nucleus reverses rapidly after drug discontinuation
by
Anthony JP, Sexton TJ, Neumaier JF.
Department of Psychiatry and Behavioral Sciences
and Harborview Medical Center,
University of Washington, Seattle 98104-2499, USA.
J Neurosci Res 2000 Jul 1;61(1):82-7


ABSTRACT

Serotonin release from dorsal raphe projections in the forebrain is regulated by terminal 5-HT(1B) autoreceptors; dysregulation of these receptors may be involved in the pathophysiology of clinical depression. Using in situ hybridization, we have previously reported that fluoxetine reduces 5-HT(1B) mRNA in rat dorsal raphe nucleus (DRN) in a time-dependent and reversible manner. In this study we examined longer term treatment (8 weeks) with several different serotonin-selective reuptake inhibitors (SSRIs) or a tricyclic antidepressant on 5-HT(1B) mRNA regulation in DRN and hippocampus, and evaluated the stability of these drugs' effects after drug discontinuation. Fluoxetine (5 mg/kg/d), paroxetine (5 mg/kg/d), sertraline (10 mg/kg/d) or nortriptyline (10 mg/kg/d) was administered to rats via subcutaneous osmotic minipumps. Paroxetine and fluoxetine reduced DRN 5-HT(1B) mRNA by 36% and 27%, respectively whereas sertraline had a no significant effect. After 3-14 days of drug washout, DRN 5-HT(1B) mRNA levels in SSRI treated rats were no longer different from control. 5-HT(1B) mRNA levels in hippocampus were not affected by SSRI drugs at any timepoint. Nortriptyline had no significant effect on 5-HT(1B) mRNA in either DRN or hippocampus. These results confirm that SSRI antidepressants reduce presynaptic 5-HT(1B) mRNA selectively, and that this effect is maintained for at least 8 weeks of antidepressant treatment but reverses rapidly after discontinuation. Furthermore, it is possible that washout after chronic antidepressant treatment, that is routinely used in functional assays of autoreceptor action in animal models, may lead to more rapid reversal of biological effects than has previously been thought
TCAs
SSRIs
5-HT1
5-HT2
5-HT3
5-HT1a
5-HT2c
Anpirtoline
Eltoprazine
Zolmitriptan
Knockout mice
5-HT2c/5-HT2b
5-HT1a v 5-HT1b
SSRIs and 5-HT1b
MDMA and 5-HT1a
MDMA and 5-HT1b
5-HT1b and reward
5-HT1b and anxiety
Aggression and serotonin
5-HT-moduline, serotonin and mood
5-HT1b inverse agonists as antidepressants


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