Role of 5-HT1A receptors in fluoxetine-induced lordosis inhibition

Jutatip Guptarak, Jhimly Sarkar, Cindy Hiegel, Lynda Uphouse

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The selective serotonin reuptake inhibitor (SSRI), fluoxetine (Prozac®), is an effective antidepressant that is also prescribed for other disorders (e.g. anorexia, bulimia, and premenstrual dysphoria) that are prevalent in females. However, fluoxetine also produces sexual side effects that may lead patients to discontinue treatment. The current studies were designed to evaluate several predictions arising from the hypothesis that serotonin 1A (5-HT1A) receptors contribute to fluoxetine-induced sexual dysfunction. In rodent models, 5-HT1A receptors are potent negative modulators of female rat sexual behavior. Three distinct experiments were designed to evaluate the contribution of 5-HT1A receptors to the effects of fluoxetine. In the first experiment, the ability of the 5-HT1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635), to prevent fluoxetine-induced lordosis inhibition was examined. In the second experiment, the effects of prior treatment with fluoxetine on the lordosis inhibitory effect of the 5-HT1A receptor agonist, (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT), were studied. In the third experiment, the ability of progesterone to reduce the acute response to fluoxetine was evaluated. WAY100635 attenuated the effect of fluoxetine; prior treatment with fluoxetine decreased 8-OH-DPAT's potency in reducing lordosis behavior; and progesterone shifted fluoxetine's dose-response curve to the right. These findings are consistent with the hypothesis that 5-HT1A receptors contribute to fluoxetine-induced sexual side effects.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalHormones and Behavior
Volume58
Issue number2
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Fingerprint

Lordosis
Receptor, Serotonin, 5-HT1A
Fluoxetine
8-Hydroxy-2-(di-n-propylamino)tetralin
Aptitude
Progesterone
Inhibition (Psychology)
Serotonin 5-HT1 Receptor Antagonists
Serotonin 5-HT1 Receptor Agonists
Bulimia
Serotonin Uptake Inhibitors
Anorexia
Sexual Behavior
Antidepressive Agents
Rodentia
Therapeutics

Keywords

  • Antidepressant
  • Hormonal priming
  • Lordosis
  • Ovariectomized rat
  • Progesterone
  • Serotonin
  • Sexual dysfunction
  • SSRIs

ASJC Scopus subject areas

  • Endocrinology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems
  • Medicine(all)

Cite this

Role of 5-HT1A receptors in fluoxetine-induced lordosis inhibition. / Guptarak, Jutatip; Sarkar, Jhimly; Hiegel, Cindy; Uphouse, Lynda.

In: Hormones and Behavior, Vol. 58, No. 2, 01.07.2010, p. 290-296.

Research output: Contribution to journalArticle

Guptarak, J, Sarkar, J, Hiegel, C & Uphouse, L 2010, 'Role of 5-HT1A receptors in fluoxetine-induced lordosis inhibition', Hormones and Behavior, vol. 58, no. 2, pp. 290-296. https://doi.org/10.1016/j.yhbeh.2010.03.003
Guptarak, Jutatip ; Sarkar, Jhimly ; Hiegel, Cindy ; Uphouse, Lynda. / Role of 5-HT1A receptors in fluoxetine-induced lordosis inhibition. In: Hormones and Behavior. 2010 ; Vol. 58, No. 2. pp. 290-296.
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