Rapid desensitization of 5-HT1A receptors in Fawn-Hooded rats after chronic fluoxetine treatment

S. Kantor, M. Graf, Z. E. Anheuer, G. Bagdy

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Anxiety, platelet serotonin (5-HT) content and functions of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) were measured in Sprague-Dawley (SD) and Fawn-Hooded (FH) rats, a strain with genetically impaired 5-HT storage and reuptake system and a putative model of depression and anxiety. In addition, the effects of 7 and 16 days treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine on 8-OH-DPAT-induced responses were studied. FH rats showed significantly higher anxiety in the social interaction test, and much lower platelet 5-HT content compared to SD rats. The efficacy of 8-OH-DPAT (15-120 μg/kg, i.v.) to induce lower lip retraction (an effect mediated by median raphe receptors) was increased in FH rats. In most FH but only a few SD rats a special neurological syndrome, clonic movement of the masseters and in-and-out movement of the eyeballs, was induced by 8-OH-DPAT, and this behaviour like other effects of 8-OH-DPAT, was completely blocked by pretreatment with the 5-HT1A receptor antagonist WAY-100635. In SD rats fluoxetine (10 mg/kg/day, i.p.) caused a moderate inhibition of 8-OH-DPAT-induced hypothermia, an effect mediated most likely by hypothalamic 5-HT1A receptors, (-19% and -40% after 7 and 16 days of fluoxetine, 24 h after the last injection, respectively). In FH rats fluoxetine caused a rapid and complete reduction in the 8-OH-DPAT-induced hypothermia (-65% and -91% after 7 and 16 days of fluoxetine, respectively). Fluoxetine caused no change in lower lip retraction but a reduction in the masseter-eyeball syndrome in both SD and FH rats. Our data provide evidence that in FH rats, median raphe 5-HT1A receptors are hypersensitive, and the hypothalamic 5-HT1A receptor desensitization, caused by SSRI antidepressants, is faster and more complete. These data support the notion that chronic treatment with SSRIs induces a desensitization of some 5-HT1A receptor populations, and impaired 5-HT storage and reuptake may accelerate this process.

Original languageEnglish
Pages (from-to)15-24
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume11
Issue number1
DOIs
Publication statusPublished - 2001

Fingerprint

8-Hydroxy-2-(di-n-propylamino)tetralin
Receptor, Serotonin, 5-HT1A
Fluoxetine
Serotonin
Sprague Dawley Rats
Induced Hypothermia
Anxiety
Serotonin Uptake Inhibitors
Therapeutics
Lip
Blood Platelets
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT1 Receptor Agonists
Psychologic Desensitization
Interpersonal Relations
hydroxide ion
Antidepressive Agents
Depression
Injections

Keywords

  • 5-HT transporter
  • 5-HT receptor
  • Anxiety
  • Depression
  • Fawn-Hooded rat
  • Hypothermia
  • Receptor desensitization
  • SSRI antidepressant

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)

Cite this

Rapid desensitization of 5-HT1A receptors in Fawn-Hooded rats after chronic fluoxetine treatment. / Kantor, S.; Graf, M.; Anheuer, Z. E.; Bagdy, G.

In: European Neuropsychopharmacology, Vol. 11, No. 1, 2001, p. 15-24.

Research output: Contribution to journalArticle

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