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Expression of Vasopressin Receptors and Oxytocin Receptors in Prairie Voles

Paper Type: Free Essay Subject: Biology
Wordcount: 1966 words Published: 8th Feb 2020

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Expression of Vasopressin Receptors and Oxytocin Receptors in Prairie Voles and their relationship with Social Behaviors

The prairie vole has served as a main interest in research regarding its uniqueness in demonstrating monogamous-related behaviors, which is a rare phenomenon in mammals. Scientists have investigated the underlying motive of these social behaviors, and have related them to two very important hormone receptors: the vasopressin receptor (V1aR) and the oxytocin receptor (OXTR), and their corresponding hormones, vasopressin and oxytocin. The variation in the expression of the V1aR gene is related to a diversity of monogamous-related behaviors in prairie voles (Barrett et al., 2013). Vasopressin receptor expression density is also related to spatial recognition, which leads to a difference in home boundaries and sexual fidelity in male prairie voles (Okhovat, Berrio, Wallace, Ophir & Phelps, 2015). In addition, the amount of expression of oxytocin receptors also lead to differences in social attachment. The expression of these receptors is controlled by regulatory elements, such as microsatellites and single nucleotide polymorphisms (SNPs) (King, Walum, Inoue, Eyrich & Young, 2016). Plenty of research has proved that various forms of regulatory elements control the expression of the V1aR and OXTR genes. In addition, various experiments have been performed where these genes have been downregulated, antagonists have been presented, and vasopressin and oxytocin hormones have been introduced to determine how these methods may affect social behavior in prairie voles (Sadino & Donaldson, 2018). The underlying genetic and epigenetic regulation of vasopressin and oxytocin receptors in monogamous prairie voles can be investigated to understand the distinct social behaviors that occur in these animals.

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The male monogamous prairie vole is an exceptional animal that demonstrates unusual social behaviors such as forming mate-pair bonds with female partners and displaying parental care. Although these behaviors are predominant in this species, about 25% of the offspring are developed outside a mate-pair bond. These encounters are termed extra-pair fertilizations (EPFs), and are due to their increased encounters with female prairie voles that are not their partner due to the male prairie voles invading other territories and having a lack of spatial memory (Okhovat et al., 2015). The avpr1a locus, which is the locus that encodes for expression of the vasopressin receptor gene, of male prairie voles with and without extra-pair fertilizations was sequenced. After sequencing was performed, it was found that single-nucleotide polymorphisms (SNPs) predicted V1aR gene expression in the retro spinal cortex (RSC), which is responsible for the spatial memory of prairie voles. Chromatin immunoprecipitation sequencing was used to target H3K4mel, a marker for enhancers, and three SNPs were found within these regions, thus showing that they are under transcriptional regulation. Monogamous prairie voles and promiscuous prairie voles differed in the expression of RSC-V1aR, with monogamous prairie voles having higher expression of RSC-V1aR. This difference in expression is correlated with sexual fidelity, due to spatial memory being responsible for the encoding of information of one’s environment and spatial orientation. The lower amount of RSC-V1aR expression corresponds to a decrease in spatial memory, which in turn leads to larger sized home ranges and increased encounter with female prairie voles that are not their partner decreasing sexual fidelity (Okhovat et al., 2015). The variation in vasopressin receptor expression in the nucleus accumbens of prairie voles is related to spatial memory, and thus, impacts social behaviors of prairie voles such as monogamy.

Variation of the vasopressin receptor in other parts of the brain, such as the ventral pallidum, may also have an impact on regulating monogamous-related behaviors including conspecific recognition and memory, territoriality, paternal care, anxiety related behaviors, and aggression. As a means to manipulate the expression of the V1aR gene, RNA interference (RNAi) was performed using short hairpin RNA sequences (shRNA), which were used to target Avpr1a locus sequences and cause down-regulation of vasopressin receptors. The control group was injected with a scrambled virus that did not target any sequence of DNA in the prairie vole. The experimental group was injected with shRNA, and this down-regulation method led to 30% reduction of V1aR expression compared to control group (Barrett et al., 2013). The exposure of the male prairie voles individuals to a female for a period of 24 hours allowed for the possible formation of mate-pair bonding in both the control group and the experimental group, which had down-regulated V1aR expression. Partner-Preference experiments, which consisted of the male prairie voles being exposed both to the females that they had been exposed to during the 24 hour mate-pair bonding period and females that were classified as “strangers,” were performed for each male prairie vole. Differences between the control group and the experimental group were demonstrated in the social behavior between groups. The experimental group spent a significantly longer amount of time with females that were not the one presented to him during the bond-formation time, demonstrating the lack of a partner preference. In comparison, the control group displayed a higher amount of social contact time spent with their partner. The two groups were also exposed to pups during a different experiment, and results showed no difference in alloparental behavior between both groups. Lastly, anxiety related behaviors were tested for in an elevated plus maze (EPM). These results showed an increased level in anxiety in the control group as compared to the experimental group (Barrett et al., 2013), which was measured by the amount of time spent in the distal opened-arm phase of the maze, with more time spend in the distal open-arm phase being an indicator of reduced anxiety. Down-regulation of the vasopressin receptor by shRNAs demonstrated a different way of how regulation of V1aR receptors directly affects social behaviors in monogamous prairie voles.

In a like manner, variation in the expression of the oxytocin receptor genes is also influenced by transcriptional regulators, and furthermore, has an impact on social behaviors of monogamous prairie voles. The nucleus accumbens (NAc) is one of the regions of the brain that influences pair bonding, and accordingly, it contains a higher density of oxytocin receptors in monogamous mammals compared to promiscuous ones (King et al., 2016). In order to determine how the expression of oxytocin receptors was controlled, a region of the Oxtr gene was sequenced and assayed. It was found that transcriptional regulators interact with polymorphic cis-regulatory elements such as the nucleotide 213739 (NT213739), which is a SNP in the intron of the Oxtr gene. This nucleotide is responsible for 74% of the variation of expression of the Oxtr gene (King et al., 2016). This number is surprisingly high as studies looking at how genetic sequences and phenotypic are explained typically report 1-10% of variance explained by a certain polymorphism. This SNP is related to the density of oxytocin receptors in the NAc. Homozygous positive prairie voles for this particular SNP showed a higher degree of partner preference, compared to heterozygous and homozygous negative prairie voles, which did not display partner preference. This genetic variation displays the necessary activation of oxytocin receptors in the creation of monogamous related behaviors such as partner preference formation in monogamous prairie voles (King et al., 2016).

In addition to the expression of vasopressin and oxytocin receptors influencing social behaviors, the hormones related to these receptors, vasopressin and oxytocin, respectfully, also have an influence on these such behaviors. It was shown that when intracerebroventricular infusion of vasopressin and oxytocin hormones was introduced in promiscuous animals, partner bonds emerged (Sadino & Donaldson, 2018). In addition, when signaling was blocked, preference was not shown in prairie voles. Vasopressin in particular is responsible for mate guarding, increased aggression, and partner preference. Vasopressin and the vasopressin receptor have to work together to modulate these behaviors in monogamous prairie voles. If one or the other is not fully functional, then the prairie vole will not display monogamous related social behaviors. This phenomenon is showed as the introduction of a vasopressin receptor antagonist resulted in the prairie vole did not show any mating induced aggression or any sort of partner preference. In addition, the high density of vasopressin receptors must be present in certain parts of the brain, such as the ventral pallidum and nucleus accumbens to be related to these behaviors. Vasopressin receptor expression is shown to be controlled by regulatory elements as previously discussed.

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As mentioned above, the studies and experiments tested out by various scientists included the genetic analysis of how vasopressin and oxytocin receptors were regulated in monogamous prairie voles. In addition, they indicated how the genetic and epigenetic regulation differences were related to their unique social behaviors. Several regulatory sections of the V1aR and Oxtr genes were manipulated and antagonists were presented to demonstrate the sufficiency and necessity for both the receptors and the corresponding hormones. All in all, the relationship between expression of the genes in certain parts of the brain and social behaviors in prairie voles has been shown to have a strong correlation. Lastly, monogamous prairie voles may be a used as model organisms in the future to investigate how these receptors and their corresponding hormones may influence social behaviors in humans, and can be used to treat social behavior disorders. For example, intranasal oxytocin may be used to treat social deficits in patients with autism disorder behavior (King et al., 2016). Although this implication must be further investigated, the prairie vole has been a great model for our understanding of the impact these genes have on social behavior.

Works Cited

  • Barrett, C. E., Keebaugh, A. C., Ahern, T. H., Bass, C. E., Terwilliger, E. F., & Young, L. J. (2013). Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles. Hormones and Behavior, 63(3), 518-526.
  • King, L. B., Walum, H., Inoue, K., Eyrich, N. W., & Young, L. J. (2016). Variation in the oxytocin receptor gene predicts brain region–specific expression and social attachment. Biological Psychiatry,80(2), 160-169.
  • Okhovat, M., Berrio, A., Wallace, G., Ophir, A. G., & Phelps, S. M. (2015). Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain. Science,350(6266),               1371-1374.
  • Sadino, J. M., & Donaldson, Z. R. (2018). Prairie voles as a model for understanding the genetic and epigenetic regulation of attachment behaviors. ACS Chemical Neuroscience,9(8), 1939-1950.


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