Evidence for accelerated desensitisation of 5-HT 2C receptors following combined treatment with fluoxetine and the 5-HT 1A receptor antagonist, WAY 100,635, in the rat

Evidence for accelerated desensitisation of 5-HT 2C receptors following combined treatment with... Both pre-clinical and clinical studies suggest that additional treatment with 5-HT 1A receptor antagonists may accelerate the antidepressant efficacy/onset of selective serotonin re-uptake inhibitors (SSRIs). Given that chronic SSRI treatment has been shown to desensitise 5-HT 2C receptor mediated responses, we have used the rat social interaction test to determine if combined treatment with WAY 100,635, a selective 5-HT 1A receptor antagonist, will accelerate this effect. In pairs of unfamiliar rats, acute administration of the 5-HT 2C receptor agonist m -chlorophenylpiperazine (mCPP) or fluoxetine decreased the time spent in social interaction, responses which were reversed by the 5-HT 2C/2B receptor antagonists SB 200646A and SB 221284. Similar reductions in social interaction were observed in rats treated with fluoxetine (10 mg/kg, i.p. daily) for 4, 7 and 14 days but was no longer apparent after 28 days of treatment. In contrast, only 7 days of combined treatment with WAY 100,635 (1 mg/kg/s.c./day) and fluoxetine were needed to reverse this response. The decrease in social interaction induced by an acute challenge of mCPP (1 mg/kg, i.p.) was also reduced after 6 days co-treatment with WAY 100,635 and fluoxetine. Thus, WAY 100,635 accelerates SSRI-induced desensitisation of 5-HT 2C receptors, suggesting that this response might contribute towards the therapeutic effects of SSRIs in man. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Evidence for accelerated desensitisation of 5-HT 2C receptors following combined treatment with fluoxetine and the 5-HT 1A receptor antagonist, WAY 100,635, in the rat

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(99)00191-4
Publisher site
See Article on Publisher Site

Abstract

Both pre-clinical and clinical studies suggest that additional treatment with 5-HT 1A receptor antagonists may accelerate the antidepressant efficacy/onset of selective serotonin re-uptake inhibitors (SSRIs). Given that chronic SSRI treatment has been shown to desensitise 5-HT 2C receptor mediated responses, we have used the rat social interaction test to determine if combined treatment with WAY 100,635, a selective 5-HT 1A receptor antagonist, will accelerate this effect. In pairs of unfamiliar rats, acute administration of the 5-HT 2C receptor agonist m -chlorophenylpiperazine (mCPP) or fluoxetine decreased the time spent in social interaction, responses which were reversed by the 5-HT 2C/2B receptor antagonists SB 200646A and SB 221284. Similar reductions in social interaction were observed in rats treated with fluoxetine (10 mg/kg, i.p. daily) for 4, 7 and 14 days but was no longer apparent after 28 days of treatment. In contrast, only 7 days of combined treatment with WAY 100,635 (1 mg/kg/s.c./day) and fluoxetine were needed to reverse this response. The decrease in social interaction induced by an acute challenge of mCPP (1 mg/kg, i.p.) was also reduced after 6 days co-treatment with WAY 100,635 and fluoxetine. Thus, WAY 100,635 accelerates SSRI-induced desensitisation of 5-HT 2C receptors, suggesting that this response might contribute towards the therapeutic effects of SSRIs in man.

Journal

NeuropharmacologyElsevier

Published: Jun 1, 2000

References

  • Activation of 5-HT 2B receptors in the medial amygdala causes anxiolysis in the social interaction test in the rat
    Duxon, M.S.; Kennett, G.A.; Lightowler, S.; Blackburn, T.P.; Fone, K.C.F.
  • Chronic fluoxetine in tests of anxiety in rat lines selectively bred for differential 5-HT 1A receptor function
    File, S.E.; Ouagazzal, A.M.; Gonzalez, L.E.; Overstreet, D.H.
  • Interaction between a selective 5-HT 1A receptor antagonist and an SSRI in vivo: effects on 5-HT cell firing and extracellular 5-HT
    Gartside, S.E.; Umbers, V.; Hajos, M.; Sharp, T.
  • Autoreceptor antagonists enhance the effect of the reuptake inhibitor citalopram on extracellular 5-HT: this effect persists after repeated citalopram treatment
    Gundlah, C.; Hjorth, S.; Auerbach, S.B.
  • Effect of 5-HT 1A receptor antagonists on citalopram-induced increase in extracellular serotonin in the frontal cortex, striatum and dorsal hippocampus
    Invernizzi, R.; Velasco, C.; Bramante, M.; Longo, A.; Samanin, R.
  • Effects of the 5-HT 2B receptor agonist, BW 723C86 on three rat models of anxiety
    Kennett, G.A.; Bright, F.; Trail, B.; Baxter, G.S.; Blackburn, T.P.
  • Anxiogenic-like effect of infusing 1-(3-chlorophenyl)piperazine (mCPP) into the hippocampus
    Whitton, P.; Curzon, G.

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