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5-HT(1A) receptor sensitivity in 5-HT(1B) receptor KO mice is unaffected by chronic fluvoxamine treatment

Christiaan H Vinkers1, Lucianne Groenink, Tommy Pattij

  • 1Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands. c.h.vinkers@uu.nl

European Journal of Pharmacology
|July 5, 2011
PubMed

Insights

Mice lacking the 5-HT(1B) receptor showed no changes in 5-HT(1A) receptor sensitivity after SSRI treatment. Chronic SSRI treatment also did not alter the stress reactivity in these mice.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genetics

Background:

  • The 5-HT(1B) receptor is implicated in mood disorders like depression and anxiety.
  • Mice lacking the 5-HT(1B) receptor (knockout mice) exhibit altered physiology and behavior.
  • Selective serotonin reuptake inhibitors (SSRIs) may affect 5-HT(1A) receptor function differently in the absence of 5-HT(1B) receptor inhibition.

Purpose of the Study:

  • To test if chronic SSRI treatment accelerates 5-HT(1A) receptor desensitization in 5-HT(1B) knockout mice.
  • To investigate the effects of chronic SSRI treatment on the hyperreactive stress response in 5-HT(1B) knockout mice.

Main Methods:

  • Chronic 21-day treatment with the SSRI fluvoxamine in wild type and 5-HT(1B) knockout mice.
  • Assessment of 5-HT(1A) receptor sensitivity using the agonist flesinoxan.
  • Evaluation of autonomic, locomotor, and behavioral responses to environmental stressors.

Main Results:

  • The stress-reducing effects of flesinoxan were similar in both genotypes before and after SSRI treatment, indicating no alteration in 5-HT(1A) receptor sensitivity.
  • Chronic SSRI treatment did not alter the exaggerated stress reactivity in 5-HT(1B) knockout mice.
  • No apparent differences in 5-HT(1A) receptor sensitivity or stress reactivity were observed between genotypes after chronic SSRI administration.

Conclusions:

  • Constitutive absence of 5-HT(1B) receptors does not lead to adaptive changes in 5-HT(1A) receptor functionality.
  • Chronic SSRI treatment does not modify the hyperreactive stress phenotype in 5-HT(1B) knockout mice.
  • These findings suggest that 5-HT(1B) receptor absence does not influence SSRI-mediated 5-HT(1A) receptor adaptations or stress responses.

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