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Sexual Preference In Rats Influenced By Oxytocin And
Dopamine
1. Introduction ………………………………………………………………………………………………………….1
2. Neurotransmitter (Dopamine)…………………………………………………………………………………….…1
2.1. Sexual motivationby dopamine…………………………………………………………………………….….2
3. General features of Oxytocinhormone……………………………………………………………………………....2
3.1. Locationofoxytocin…………………………………………………………………………………………...2
3.2. Factors affectingthe release of oxytocin……………………………………………………………………....2
3.3. Sexual preference due to oxytocin……………………......................................................................................3
4. Partner preference test………………………………………………………………………………………………..3
4.1. Table andgraphs of concentrations andeffects onsexual behavior of rats. ………………………………..... 6
4.2. Results of different experiment…………………………………………………….…………………………..6
5. Conclusion………………………………………………………………………………………………………..…..7
6. References………………………………………………………………………………………………………........8
1. ITRODUCTION
Dopamine is a brain neurotransmitter that plays an important role in sexual preference or
motivation behavior. The process of having sex reinforces sexual preference between males and
females after the brain releases huge levels of dopamine (DA) during the act and giving the rat a
happy hit and conditioning the animal's preference for its mate. The preferential sexual behavior
by dopamine backed up almost immediately after ejaculation, at the time when the male's brain
is flooded with the hormone oxytocin. It is thought that the theses two chemicals induce the rats
toward their social attachment to their mate by increasing their trust and inducing a state of calm.
The first aim of the present work is to assess the behavioral response in female rat, with
particular attention to certain aspects of sexuality and concentration level of dopamine and
oxytocin in their body. As it has been demonstrated that central dopamine is the main
neurotransmitter of preferential sexual behavior. The release of DA is modulated by systematic
particular level of oxytocin.
2. Neurotransmittor Dopamine(DA):
In animals, dopaminergic agonists tend to enhance sexual activity. This has implicated dopamine
in appetitive versus copulatory components of sexual behavior in rats. These effects are complex
and may vary according to the brain region and type of dopamine receptor that is affected due to
dopamine level. it plays an important role in milk production and inhibitory effects on prolactin
release. Besides this, dopamine may have a facilitatory effect on oxytocin (OX) release in rats.
Dopamine injections, given centrally can excite the pulsive oxytocin release in rats. High
dosages of dopamine produce a sustained release of hormones from the posterior part of pituitary
gland. The dopaminergic synapses have been identified in conjunction with oxytocin during
studies in rats. DA also inhibit the release of oxytocin, this indicating that the interactions among
dopaminergic and oxytocinergic processes in rats are complex.
2.1. Dopaminergic systems of possible importance for preferncial sexual behavior:

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dopamine outside the central nervous system may participate in seminal emission. Dopamine D1
and D2 receptors are found in rat seminal vesicles, and dopamine applied locally to these organs
enhances contractile activity. A dopamine antagonist not easily penetrating the blood–brain
barrier, domperidone, does not affect penile reflexes or preferential copulatory behavior. There is
no indication that dopamine receptors outside of the central nervous system modify female
sexual behavior.
2.2. Sexual motivation by dopamine:
Sexual motivation is usually defined as an individual’s urge to seek sexual contact with another
individual of the opposite sex. The intensity of sexual motivation has been assessed in many
ways. Usually, the rate of execution of some kind of instrumental response has been taken as an
indicator of level of motivation.
Several studies with dopaminergic compounds have indeed employed rate of responding as the
critical variable. Some have quantified the number of lever presser per unit time with access to a
receptive female as reinforcement. Others have used running speed in a straight alley with a
receptive female in the goal box as the measure of motivation.
3. General Features of Oxytocin
The oxytocin is a nonapeptide characterized by a six amino acid ring structure with a three amino
acid tail. Oxytocin is produced primarily in the supraoptic (SON) and paraventricular (PVN)
nuclei of the hypothalamus. Pulses of oxytocin are released into the systemic circulation at the
posterior pituitary. Oxytocin is secreted into the circulation in conjunction with its carder protein
(neurophysin).
The half-life of peripheral or centrally injected oxytocin is species specific and the half-time for
clearance in CSF is approximately 19 minutes in rats. oxytocin is released into the central
nervous system where it presumably affect neuronal activity. Oxytocin does not pass easily
through the blood-brain barrier, but there is evidence of bidirectional transport of small amounts
of oxytocin between the general circulation and cerebrospinal fluid.
3.1. Localization of Oxytocin
Most of the centrally located oxytocin is found in large magnocellular neurons located in the
paraventricular nucleus of hypothalamus and supraoptic nucleus (SON); these cells project to the
posterior pituitary gland where oxytocin is stored and secreted into the systemic circulation.
Smaller, parvocellular cell bodies containing oxytocin also have been identified in the PVN. The
OT fibers originating in the parvocellular neurons extend into other parts of the nervous system
including the caudal brain stem and spinal cord. Oxytocin receptors have been identified in a
variety of neural tissues that includes the ventromedial hypothalamus (VMH), bed nucleus of the
stria terminalis (BNST), central amygdala, lateral septum, anterior olfactory nucleus ventral
subiculum, and dorsal motor nucleus of the vagus Patterns of oxytocin receptors and relative
concentrations of these receptors are species specific.

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3.2. Factors Regulating the Release of Oxytocin
Using the rat as a model, the factors responsible for the release of oxytocin have been studied
extensively in the analysis of mechanisms underlying lactation and parturition. In these contexts,
breast and genital stimulation are potent releasers of oxytocin reflex. The release of oxytocin can
also be induced even in anesthetized male rats by touch of light, pinch or electrical stimulation.
Olfactory tract stimulation and olfactory stimuli can release oxytocin in some species. Oxytocin
release also can become conditioned, permitting release by cognitive stimuli, at least during
lactation. In rats, olfactory input also has been implicated in anatomical changes within the SON
that accompany lactation. Oxytocin can stimulate its own release in rats. The opiates, serotonin
and gamma aminobutyric acid (GABA), may also inhibit the release of oxytocin.
3.3.Oxytocin and Preferential Behavior:
Oxytocin, is secreted by the posterior pituitary that has powerful contractile effects on smooth
muscle such as that found in the uterus of mamals. Oxytocin was described first as a "female"
reproductive hormone with critical actions in parturition and lactation.
4. PARTNER PREFERENCE TEST
This test was carried out by taking three-chamber testing apparatus consisted of a neutral cage
(20 cm high×50 cm long×40 cm wide) joined by plastic tubes (7.5×16 cm) of two parallel
identical cages, each housing a stimulus animal. The female subjects were free to move
throughout the apparatus. The stimulus males were tethered in their cages and direct movement
was restricted to stop the contact with each other. The two male rats i.e. the partner which was
familiar (the male that had previously been housed with the subject) and a conspecific stranger
male (a male that had not previously encountered the subject) were there as stimulus in
experiment. After the subjects were placed into the neutral cage, their behavior was recorded for
3 h with a time-lapse VCR (instrument).
4.1. Data quantification and analysis:
For determining the partner preference, duration and frequency of the subject’s side-by-side
contact with either the partner or with stranger were recorded.
The partner preference is defined as subjects spending significantly more time in body contact
with the partner versus stranger, as determined by a t-test (P<0.05). The Video tapes of the 6 h of
cohabitation were reviewed to confirm the absence of mating. Beside that as drug effects on
partner preferences could be secondary to effects on locomotive activity during the preference
test the group differences in the frequency of subject’s cage entries were analyzed by a one-way
analysis of statistical variance.

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4.2.Study I: How Dopamine and oxytocin interact to regulate partner Preference
formation?
Previous studies have explained that, in female rat, administration of OTA or the D2-type DA
receptor antagonist, eticlopride, blocks mating-induced partner preferences whilethe
administration of Oxytocin or the D2-type Dopamine receptor agonist which induces this
behavior in the absence of mating in rats. Beside that these data dexplained Oxytocin and
Dopamine involvement in partner preference formation of rats and it is still to know whether the
two interact to regulate social attachment.
Procedures:
For experiment 1a, subjects were implanted with guide cannulae aimed at the lateral ventricle.
After 3 days of recovery, the subjects were randomly assigned to one of four treatment groups.
Group 1 (control), subjects received i.c.v. administration of CSF (200 nl) and i.p. injection of
saline (200 micro liter; n=7). Subjects of group 2, received administration of CSF and saline
containing 5 micro gram quinpirole (n=7). Subjects of group 3, received administration of CSF
and saline containing 5 micro gram quinpirole with 50 _g eticlopride (n_8). In group 4, subjects
received CSF containing 50 ng OTA and saline containing 5 micro gram quinpirole (n=8). These
doses (and doses in the following experiments) were chosen because they effectively induced or
blocked partner preference formation in female rat in previous studies.
After the administration of drug, subject rats were housed with a male for 6 h in the absence of
mating followed by the partner preference test in experiment. All of the subjects then were
anesthetized and killed, the cannulation sites in their brains were verified histologically. While in
experiment 1b, subject rats were implanted with osmotic minipumps aimed at the lateral
ventricle. They then were randomly assigned to one of four treatment groups that received i.c.v.
infusions of either CSF alone (0.5 micro l/h; n=7) or CSF containing OT (1 ng/micro l; n=9),
Oxytocin (1 ng/micro l) with OTA (10 ng/_l; n=11), or OT (1 ng/micro l) with eticlopride (10
ng/micro l; n=8). After overnight recovery each subject rat was housed with a male for 6 h in the
absence of mating, followed by the partner preference test as was in first. The Subjects then were
killed and infusion sites were verified histolitically.
Results:
In experiment 1a, control females was exhibiting approximately equal side-by-side contact with
the partner or the stranger after 6 h of cohabitation (Fig. 1). Females injected with the D2-type
receptor agonist, quinpirole, spent significantly more time preferentially with the partner than
with the stranger (t=2.88, P<0.05) male. This quinpiroleinduced behavior was blocked by co-
administration of either the D2-type receptor antagonist, eticlopride or OTA, suggestive of that
access to both oxytocin and D2-type receptors was necessary for quinpirole induction of partner
preference formation.

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In experiment 1b, control females did not show partner preferences whereas females infused with
Oxytocin spent significantly more time with the partner than with the stranger (t=2.68, P<0.05;
(Fig. 2). Co-administration of oxytocin with either OTA or the D2-type antagonist, eticlopride,
did not induce this behavior, suggesting that blockade of either type of receptor prevented
oxytocin-induced partner preference formation. In both experiments, no group differences were
found in the frequency of subject’s cage entries during the partner preference test (Table 1).

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4.3.Study II:The NAcc an important brain area for DA-OT regulation of partner
preference formation?
From the study I it is demonstrated that oxytocin and dopamine interact in the regulation of
partner preferences in female rats. Previous studies have shown that NAcc contains both
oxytocin and dopamine receptors. And activation of either oxytocin or dopamine D2-type
receptor in NAcc is involved in partner preference formation. the present study, tested the
hypothesis that NAcc is a brain area where oxytocin and dopamine interact to regulate partner
preferences in female rats.
Procedures.
In experiment 2, female rats were implanted with guide cannulae bilaterally aimed at NAcc. The
subjects rats then were randomly assigned to one of seven treatment groups and received one of
the given injections: CSF alone (210 nl per side; n=8), CSF containing 0.001 ng (n=13), 0.02 ng
(n=7), 0.2 ng (n=9), or 2.0 ng (n=10) of quinpirole, or CSF containing 2.0 ng quinpirole with
10.0 ng eticlopride (n=12) or with 11.0 ng OTA (n=12). In the eighth group (n=5), subjects were
implanted with guide cannulae bilaterally aimed at the caudate putamen and then injected with
1.5 ng quinpirole.
Just after drug administration, all subjects were housed with males for 6 h without mating
followed by a partner preference test. After that subjects were killed and their brains were
sectioned from cannulation sites to examine.
Results:
Histological verification illustrated that most injection sites were located in the shell of the
NAcc. In experiment 2a, females that received injections of CSF (control) or lower doses of
quinpirole (0.002 or 0.01 ng) did not show partner preferences (Fig.3). But the females that
received injections of higher doses of quinpirole showed significantly more side-by-side contact
with the partner than with a stranger (t=2.60, P<0.05 for 0.1 ng quinpirole and t=3.32, P<0.01 for
1.0 ng quinpirole). Injections of the D2-type receptor antagonist, eticlopride, or OTA into NAcc

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blocked quinpirole-induced partner preferences. Further, quinpirole’s effect on behavior seemed
to be site-specific because administration of quinpirole into the caudate putamen did not induce
partner preference formation. There were no treatment effects found in animals during the
partner preference test.
5. CONCLUSION:
Experimental study showed that the administration of oxytocin or dopamine induces partner
preference formation in female rats in the absence of mating partner. the results obtained from
the present study not only confirmed but also extended these findings demonstrating that access
to both oxytocin and dopamine D2-type receptors is necessary for partner preference formation
in rats. It is also found that NAcc is a brain area important for oxytocin-dopamine interaction in
rats. Particularly blocking of oxytocin receptors in NAcc blocked partner preferences induced by
the D2-type agonist whereas blockade of D2- type, but not D1-type, dopamine receptors
prevented partner preference formation induced by oxytocin. In conclusion, in both studies drug
administration had no significant effects on the animal’s locomotor activity during the preference
test that indicating the treatment effect on pair bonding was not an artifact of hyper or hypo
activity. Collectively, these results suggest that concurrent activation of oxytocin and D2-type
dopamine receptors in NAcc is essential for pair bond formation in female rats.
A lot of literature has demonstrated behaviorally relevant interactions between neuromodulator
(such as oxytocin) and neurotransmitter (such as dopamine) systems. OT–DA interactions have
been implicated in several behaviors including yawning, penile erections and mating and such
interactions in NAcc, in particular, are found to regulate grooming and cocaine- induced
locomotor hyperactivity. Here, for the first time, we show evidence that OT–DA interactions are
also important for complex social interactions most importantly the formation of social bonds for

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monogamous mammals like in rats. We found that local administration of a D2-type agonist or
OT in NAcc induced partner preference formation in a region-specific and supporting the notion
that NAcc is a brain area important for DA and OT regulation of pair bonding.
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