|LETTER TO THE EDITOR
|Year : 2013 | Volume
| Issue : 4 | Page : 412-414
Chronic fluoxetine treatment and sexual behavior in male and female albino rats
Ranjita Santra1, Patralekha Raychaudhuri2, Chiranjib Bagchi2, Santanu Kumar Tripathi2
1 Department of Pharmacology, Nilratan Sircar Medical College, Kolkata, India
2 Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India
|Date of Web Publication||15-Jul-2013|
Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Santra R, Raychaudhuri P, Bagchi C, Tripathi SK. Chronic fluoxetine treatment and sexual behavior in male and female albino rats. Indian J Pharmacol 2013;45:412-4
|How to cite this URL:|
Santra R, Raychaudhuri P, Bagchi C, Tripathi SK. Chronic fluoxetine treatment and sexual behavior in male and female albino rats. Indian J Pharmacol [serial online] 2013 [cited 2020 Jul 10];45:412-4. Available from: http://www.ijp-online.com/text.asp?2013/45/4/412/115004
The role of the serotonergic system in influencing sexuality is well known.  One of the most prominent adverse effects of the selective serotonin reuptake inhibitor (SSRI) antidepressants is sexual dysfunction, as seen in the clinical setting and also in animal experiments. ,, However, controversies and contradictions do exist.  As depression itself is also known to adversely affect sexual behavior,  it is difficult to implicate SSRIs to have contributed partly or wholly to such problems. Human sexuality is a hugely complex phenomenon. Nonetheless, sexual physiology in general has been phylogenetically conserved, thereby enabling the successful use of suitable animal models in studying the same. 
Thus, it seems that the association between chronic fluoxetine therapy and sexual behavior has not been adequately probed in animal models, as there is a relative paucity of literature in this regard. We, therefore, planned the present study to investigate the effect of fluoxetine on the sexual behavior of male albino rats and on the estrus cyclicity vis-a-vis the behavioral estrus in female rats.
A total of 35 adult albino rats, selected on the basis of fulfillment of the screen criteria of behavioral estrus positivity for the females and presence of sexual activity for the males, were employed for the study. The test group comprised of 18 rats - nine each of male and female, and a control group of eleven rats - five male and six female. The remaining six rats, three male and three female were used as 'intruders,' while the rat of the opposite sex, belonging to the test or the control groups, the sexual behavior of which was studied, acted as the 'resident'. Rats of the opposite sex were separately caged. All the animals were allowed free access to standard food and water ad libitum. The housing and handling of animals and conduct of the experiment strictly followed the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines. The study was duly approved by the Institutional Animal Ethics Committee (IAEC).
The rats in the test group were treated with intraperitoneal fluoxetine, dissolved in normal saline, at a dose of 10 mg / kg body weight daily,  for six weeks. The controls were given an equivalent volume of normal saline. The defined sexual behavior parameters of both male and female rats were noted for seven consecutive days prior to the onset of fluoxetine treatment (baseline or pretreatment) and during the second, fourth, and sixth week of fluoxetine treatment. Each rat was observed for 10 minutes, during the dark phase of the light-dark cycle of a day, for any explicit sexual behavior,  in the presence of an intruder rat of the opposite sex. The presence of any given parameter in each individual rat, male or female, on any day of the preceding week was considered positive and computed as baseline data, with bi-weekly follow-up recordings for that parameter. The estrus behavior of the female rats was determined by considering the presence of any of the different female sexual behavior parameters like solicitation, ear wiggling, lordosis, or allowing mounting (by the intruder male). On the other hand, the males displayed various signs of sexual behavior, for example, anogenital sniffing, climbing, grooming, roaming, rearing, self-licking, and mounting over the intruder female rat.  The characteristic microscopic features in the vaginal smear collected during different phases of the estrous cycle were studied for one week before the onset of fluoxetine treatment (pretreatment) and in the seventh week (after a six-week treatment) to assess the impact of prolonged fluoxetine therapy.
Data were expressed in the number and percentages of albino rats showing positive sexual behavior. Comparison between the test and control groups, in both male and female rats, was done by the Chi-square test and Fisher's exact test as and when applicable, whereas, within-group comparison at different time points was done by the McNemar test. Compared to the baseline, pairwise within-group comparison in female rats [Table 1] showed significant reduction in the behavioral estrus (p = 0.008) only during the sixth week of fluoxetine treatment [McNemar test]. Different phases of vaginal estrous are characterized mainly by the presence of nucleated epithelial cells (pro estrus and early estrus), large conified epithelial cells (estrus), appearance of leukocytes together with some cornified epithelial cells (metestrus), and predominantly leukocytes with some epithelial cells (diestrus). 
|Table 1: Comparison of the positive behavioral estrus of female albino rats in two treatment groups|
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In this study, comparison of the pre- versus post-treatment vaginal smear cytology could not show any discernible difference in any of the estrus phases.
In the male rats, fluoxetine treatment showed a discernible change in some sexual behavior parameters. Statistically significant reduction in positive sexual behavior was observed [Table 2] for the following parameters: Anogenital sniffing (p = 0.031 at the sixth week), climbing (p = 0.008 both at the fourth and sixth weeks), grooming (p = 0.016 at the sixth week), roaming (p = 0.031 both at the fourth and sixth weeks), and self-licking (p = 0.008 at the fourth and p = 0.016 at the sixth week) [McNemar test]. When compared to the controls, the treated animals showed a decrease in sexual behavior [Table 2], in particular reference to anogenital sniffing (p = 0.003 at the fourth week, p = 0.027 at the sixth week), climbing (p = 0.003 both at the fourth and sixth weeks), grooming (p = 0.021 at the sixth week), and self-licking (p = 0.023 at the fourth week), indicating the impact of chronic fluoxetine treatment [Fisher's exact test]. However, whether compared to the baseline values or to the corresponding values in the control group, a minimum of four weeks of fluoxetine treatment was required to bring about significant changes.
|Table 2: Comparison of the positive sexual behavior of male albino rats in two treatment groups|
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The results of this preliminary study are consistent with the findings of an earlier study by Matuszcyk et al., where subchronic administration of fluoxetine in normally cycling female rats caused significant reduction in the behavioral estrus, yet retaining the vaginal estrous. On the other hand, our observation that similar treatment in the sexually active male rats resulted in a significant deterioration in sexual function, conforms to another report by the same group of workers. 
However, further studies are needed to fully understand the clinical implications of our findings, as also to investigate the possible mechanisms involved in the fluoxetine-induced worsening of sexual behavior in males and females.
| » References|| |
|1.||Meston CM, Frohlic PF. The Neurobiology of Sexual Function. Arch Gen Psychiatry 2000;57:1012-30. |
|2.||Rosen RC, Lane RM, Menza M. Effects of SSRIs on sexual function: A critical review. J Clin Psychopharmacol 1999;19:67-85. |
|3.||Matuszcyk JV, Larsson K, Eriksson E. The selective serotonin reuptake inhibitor fluoxetine reduces sexual motivation in male rats. Pharmacol Biochem Behav 1998;60:527-32. |
|4.||Matuszczyk JV, Larsson K, Eriksson E. Subchronic administration of fluoxetine impairs estrous behavior in intact female rats. Neuropsychopharmacology 1998;19:492-8. |
|5.||Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol 2009;29:157-64. |
|6.||Fausto-Sterling A. Animals models for the development of human sexuality: A Critical Evaluation. J Homosexual 1995;28:217-36. |
|7.||Agmo A, Turi AL, Elligsen E, Kaspersen H. Preclinical models of sexual desire: Conceptual and behavioral analyses. Pharmacol Biochem Behavior 2004;78:379-404. |
|8.||Marcondes FK, Bianchi FJ, Tanno AP. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 2002;62:609-14. |
[Table 1], [Table 2]