Role of 5-HT(1A) receptors in fluoxetine-induced lordosis inhibition.

Abstract

The selective serotonin reuptake inhibitor (SSRI), fluoxetine (Prozac(R)), 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-HT(1A)) receptors contribute to fluoxetine-induced sexual dysfunction. In rodent models, 5-HT(1A) receptors are potent negative modulators of female rat sexual behavior. Three distinct experiments were designed to evaluate the contribution of 5-HT(1A) receptors to the effects of fluoxetine. In the first experiment, the ability of the 5-HT(1A) 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-HT(1A) 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-HT(1A) receptors contribute to fluoxetine-induced sexual side effects.

• Authors: Jutatip Guptarak, Jhimly Sarkar, Cindy Hiegel, Lynda Uphouse
• Journal: Hormones and behavior (Horm Behav) Vol. 58 Issue 2 Pg. 290-6 (Jul 2010) ISSN: 1095-6867 [Electronic] United States
• PMID: 20223238 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Inc. All rights reserved.

Chemical References

• Piperazines
• Pyridines
• Serotonin 5-HT1 Receptor Agonists
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin Antagonists
• Serotonin Receptor Agonists
• Serotonin Uptake Inhibitors
• Fluoxetine
• Receptor, Serotonin, 5-HT1A
• Progesterone
• N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
• 8-Hydroxy-2-(di-n-propylamino)tetralin

Topics

• 8-Hydroxy-2-(di-n-propylamino)tetralin (pharmacology)
• Animals
• Dose-Response Relationship, Drug
• Female
• Fluoxetine (administration & dosage, adverse effects, pharmacology)
• Models, Animal
• Ovariectomy
• Piperazines (pharmacology)
• Progesterone (metabolism)
• Pyridines (pharmacology)
• Rats
• Rats, Inbred F344
• Receptor, Serotonin, 5-HT1A (metabolism)
• Serotonin 5-HT1 Receptor Agonists
• Serotonin 5-HT1 Receptor Antagonists
• Serotonin Antagonists (pharmacology)
• Serotonin Receptor Agonists (pharmacology)
• Selective Serotonin Reuptake Inhibitors (administration & dosage, adverse effects, pharmacology)
• Sexual Behavior, Animal (drug effects, physiology)
• Sexual Dysfunctions, Psychological (chemically induced, drug therapy, metabolism)
• Time Factors