Electronic Journal of Pharmacology and Therapy Vol. 2, 35-38 (2009)
ISSN: 0973- 9890 (Available online at
EFFECT OF TADALAFIL ON SEXUAL BEHAVIOR IN FEMALE RATS
ASWAR URMILA, M. AND BODHANKAR SUBHASH, L.
Department of Pharmacology, Bharati Vidyapeeth University, Erandawane, Paud Road,
Received: April 15, 2009; Accepted: May 20, 2009
Abstract: The objective of the study was to evaluate and compare the effects of tadalafil and
sildenafil on sexual behavior in female rats. Female Wister rats (180 ± 10 g) showing estrous
phase were selected. The rats were divided into three groups (n=6). Group I was given vehicle,
group II was administered tadalafil (10 mg/kg p.o.) and group III was given sildenafil (10 mg/kg
p.o.). Drugs were administered to female rats one hour before copulatory behavior studies. They
were placed individually with male rat of proven fertility in a Plexiglass chamber. The female
sexual behavior was observed for 30 min. Our study indicated that tadalafil and sildenafil both
significantly decreased darting, hopping and lordosis latencies. Both increased darting hopping,
lordosis frequencies, anogenital grooming and licking behavior. Tadalafil was superior to
sildenafil in increasing lordosis duration. The results obtained in our study differentiated the
effects of tadalafil than sildenafil especially in consumatory phase of sexual behavior. Weak
effect of sildenafil in improving lordosis frequency and duration observed in present study may
be correlated with failure of sildenafil in clinical trials.
Female sexual dysfunction, Lordosis, Tadalafil
that mediates smooth muscle relaxation and bloodengorgement . The duration of action of cGMP is
Female sexual dysfunction (FSD) is a new, rapidly
controlled by phosphodiesterase (PDE) enzyme
expanding area of sexual medicine. It is multicausal
activity of which PDE5 is the major player in the
and multidimensional disorder, which results in
penis. The first PDE5 inhibitor for the treatment of
significant personal distress, adversely impacting on
male erectile disorder, sildenafil (Viagra), was
life quality and interpersonal relationship. Current
launched in 1998 and was followed by vardenafil
epidemiological data reveal that up to 43 % of woman
(Levitra) and tadalafil (Cialis). Following the enormous
has some type of sexual dysfunction. Approxima-
success of PDE5 inhibitors in male, the attention was
tely 10 million American women aged 50-74 years
focused on female sexual dysfunction. In common
complaints diminished vaginal lubrication, pain and
with the penis, the clitoris is derived from the same
discomfort with intercourse, decreased arousal and
embr yonic stem cells and possesses corpus
difficulty achieving orgasm. Lauamnn et al.  found
cavernosal tissue. During female arousal, the vagina
that sexual dysfunction is more prevalent in woman
also becomes engorged. The presence of PDE5 in
than in men and is associated with var ious
woman’s clitoral and vaginal tissue [3,4], relaxation
psychodemographic characteristics such as age,
of human vaginal smooth muscle strips [5,6] and
education and poor physical and emotional health.
increase blood flow into dog vagina and clitoris iswell reported in literature.
Male penile erection occurs following the release ofthe neurotransmitter nitric oxide, which results in
Caruso et al.  has reported that sildenafil 25 and
cyclic guanosine monophosphate (cGMP) production
50 mg/kg significantly improved sexual function i.e.
increased arousal, orgasm, enjoyment, satisfaction,
to 55 % under 12:12-h light dark cycle. The animals
frequency of intercourse and frequency of fantasies
had free access to food pellets (Chakan Oil Mills,
in premenopausal (22-28 yrs) woman. These
Pune, India) and water was given ad libitum
investigators noted that 70.5 % of women in the study
experimenta l prot ocol wa s approved by the
wanted to continue treatment with sildenafil. In
Institutional Animal Ethics Committee (IAEC) of
contrast to this, several large scale, placebo controlled
Poona College of Pharmacy, Pune, constituted under
studies including about 3000 women with female
Committee for the Purpose of Control and Supervision
sexual arousal disorder by the pharmaceutical
company Pfizer, showed inconclusive results on theefficacy of sildenafil.
: Female Wister rats (180 ±
10 g) showing estrous phase were selected. The rats
Tadalafil, a Phophodiesterase 5 inhibitor, enables men
were divided into three groups (n=6). Group I was
with erectile dysfunction to achieve and maintain an
given vehicle, group II was administered tadalafil (10
erection sufficient for successful intercourse with
mg/kg p.o.) and group III was given sildenafil (10
sexual stimulation . Its chemical structure differs
mg/kg p.o.). Drugs were administered to female rats
significantly from sildenafil . Tadalafil (20 mg)
one hour before copulatory behavior studies.
produces penile rigidity within 25-30 minutes. Theplasma half life of tadalafil amounts to be 17.5 hours
Effect on sexual behavior :
. The effect of tadalafil on sexual behavior in
Wister rats (200-250g) were used for the study. The
normal female rats, however, has not been reported.
rectangular wooden box with plexiglass front and wire
The objective of the study was to investigate the
mesh top was used for the observations. One male
effects of tadalafil and sildenafil on sexual behavior
rat was then placed five minutes before introduction
of female. The observations were made for 30minutes. The study was carried out at 2200-2400
MATERIALS AND METHODS
hrs under dim white light (30 lux). Sexual behavior infemale rats was studied by the methods described
Sildenafil (Verma Pharmaceuticals,
by Giuliano et al. . Sexual behavior was divided
Pune) was obtained as gift sample, and tadalafil
into prospective and receptive components.
(Macleodes Pharmaceutical Ltd.,Mumbai), waspurchased from market.
Proceptive behavior parameters:
hopping and orientational activities were observed
Female Wistar rats of weight range 180 ±
carefully. Dating is a short run where female abruptly
10 g and male Wistar rats (200-250g) were purchased
stops presenting her posterior to male. Hopping is a
from National Toxicology Centre, Pune, India and
short jump with stiff legs followed by immobility and
used for the study. They were maintained at a
presentation and orientational activities are anogenital
temperature of 25 ± 1 °C and relative humidity of 45
grooming, genital grooming and licking behavior.
Effect of tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) on darting, hopping and lordosis latencies. Figure in
parenthesis represents dose. Data represented are mean ± S.E.M (n=6) analysed by one way ANOVA followed by post hoc
Dunnets t test. #p<0.0001
Effect of tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) on darting, hopping and lordosis frequencies. Figure in
parenthesis represents dose. Data represented are mean ± S.E.M (n=6) analysed by one way ANOVA followed by post hoc
Dunnets t test. #p<0.0001
Effect of tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.) on lordosis interval, anogenital grooming, genital grooming
and licking behavior in female rats. Data represented are mean ± S.E.M in female rats (n=6) analysed by one way ANOVA followed
by post hoc
Dunnets t test. #p<0.0001, **p<0.001.
Receptive behavior parameters
: Lordosis -
showed 4.17 ± 0.60 hops and sildenafil (10 mg/kg
behavior posture assumed by female to allow
p.o.) treated animals showed 5.83 ± 0.95 hops.
mounting by male was also carefully examined.
Treatment with sildenafil and tadalafil increasednumber of hops significantly (p<0.0001). (Table 2).
Data for each of the parameter
was analyzed by one-way ANOVA followed by
The time taken to achieve lordosis
Dunnets post hoc test using Graph Pad, Prism
by female rats in control group was 1170 ± 96.436
seconds where as in tadalafil (10 mg/kg p.o.) groupit was 340 ± 42.89 seconds. In sildenafil (10 mg/kg
p.o.) treated rats the lordosis latency was 488.83 ±73.08 seconds. The lordosis latency was significantly
The time taken to initiate the short
reduced in sildenafil and tadalafil treated group
run made by female rats in front of male exposing
their posterior was considered as darting. The dartinglatency observed in control group was 628.33 ±
Lordosis frequency and duration:
132.97 seconds, while that of tadalafil (10 mg/kg p.o)
frequencies in female rats were control 1.0 ± 0.0,
and sildenafil group it was 83.33 ± 14.29.seconds
tadalafil (10 mg/kg p.o.) treated group it was 3.0 ±
and 218.33 ± 36.37 seconds respectively. The tadalafil
0.26 while in sildenafil group (10 mg/kg p.o.) it was
and sildenafil group showed significantly (p<0.0001)
1.66 ± 0.33. The lordosis frequency was significantly
less latency period as compared to control group.
(p<0.0001) high in sildenafil and tadalafil treated
Tadalafil was more effective in reducing darting
group. The duration of lordosis was significantly
latency compared to sildenafil group. (Table 1).
(p<0.001) more in tadalafil treated group thansildenafil group. (Table 3).
The number of darting recorded
for 30 minutes period 1 hour after administration of
Sildenafil (10 mg/kg p.o.)
drugs in control group was 6.5+1.23 while that of
and tadalafil (10 mg/kg p.o.) significantly increased
tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg p.o.)
anogenital grooming (p<0.001) compared to control
group was 15.33+0.76, 8.33+1.23 respectively. The
darting frequency was significantly higher in tadalafilgroup and sildenafil group (p<0.0001) than control
No significant increase was
observed in sildenafil (10 mg/kg p.o.) and tadalafil(10 mg/kg p.o.) group as compared to control group.
Hopping is characterized by a
short jump with stiff legs followed by immobility anda presenting behavior. Hoping latency seen in control
Sildenafil (10 mg/kg p.o.) and tadalafil (10
rats was observed to be 900 ± 120.99 seconds while
mg/kg p.o.) significantly increased licking behavior
in tadalafil (10 mg/kg p.o.) and sildenafil (10 mg/kg
(p<0.001) compared to control group. (Table 3).
p.o.) group it was found to be 350.0 ± 44.94, 298.0 ±54.92 seconds respectively. The hopping latencies
were significantly decreased by both tadalafil andsildenafil (p<0.0001). (Table 1).
Gonadally intact female rats of reproductive age gointo sexual heat every hour to five days immediately
Control group exhibited 1.83
after ovulation. This process is imitated by the
± 0.30 hops, tadalafil (10 mg/kg p.o.) treated group
sequential actions of the estrogen and progesterone
in brain and periphery, so that sexual behavior shows
behavior parameters like genital stimulation,
an “estrous cycle” . Peripheral sexual reflexes,
masturbation, copulation and orgasm in human female
copulatory behavior, and appetitive conditioned sexual
. The results obtained in our study differentiated
responses have been examined in female rats, rabbits,
the effects of tadalafil than sildenafil especially in
and primates such as macaques. The physiologic
consumatory phase of sexual behavior. Weak effect
mechanisms that regulate vaginal blood flow are
of sildenafil in improving lordosis frequency and
extremely similar between species, and more is
duration observed in present study may be correlated
known about the hormonal and neural regulation of
with failure of sildenafil in clinical trials.
the reflexive posture lordosis than any other sexualreflex .
It is concluded that tadalafil improved consumatorybehavior especially higher lordosis frequency and
Female sexual behavior can be divided into sequential
duration compared to sildenafil. The beneficial effects
precopulatory and consumatory components. In the
of tadalafil on female sexual disorder needs to be
female rats these aspects of sexual behavior are also
referred to as proceptive and receptive component,two different aspects of sexual behavior are displayed
by estrous females in the presence sexually activemales . To solicit attention and approach of male,
 Lauamnn, E., Paik, A. and Rosen, R.: JAMA, 281:
female displays variety of active proceptive behavioral
patterns including solicitation, hops, anogenital
 Ballard, S., Gingell, C., Tang, K., Turner, L., Price, M.
grooming, licking the male partner and darts. In the
and Naylor, A.: J. Urol., 159: 2164-2171 (1988).
 Amati, G., di Gioia, C.R.T., Bologna, M.,.Giordano,
present study tadalafil improved proceptive factor of
D., Giorgi, M., Dolci, S., and Jannini, E.A.: Urology,
sexual behavior in female rats more effectively than
sildenafil. Enhancement of proceptive behavior i.e.
 Oelke, M., Hedlund, P., Albrecht, K., Ellinghaus, P.,
decrease in darting and hopping latency and increase
Stief, C., Jonas, U., Andersson, K., and Uckert, S.:
in darting and hopping frequency also increase in
Anogenital grooming while decrease in genital
 Uckert, S.: World J. Urology., 23: 398-404 (2005).
grooming and increase in licking tendency correlate
 Angulo, J., Cuevas, P., Cuevas, B., Bischoff, E.
well with precopulatory behavior in human female.
and Sáenz de Tejada, J.: Int J. Impot Res., 15: 137-
Receptivity has been used to describe the behavioral
postures assumed by females to allow mounting by a
 Caruso, S., Intelisano, G., Lupo, L. and Agnell, C.: Br
J. Obstet Gynaecol., 108: 623-628 (2001).
male with the lordosis reflex being the best known
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and most studied response. Tadalafil also showed
Jemmice, F.: Diabetes Care, 25: 2159-2164 (2002).
improvement of lordosis duration and frequency as
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compared with sildenafil moreover the duration of
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 Uckert, S., Hedlund, P., Andersson, K., Truss, M.,
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Interg. Comp Physio., 281 (1): 140-149 (2001).
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