The role of oxytocin in male and female reproductive behavior
Introduction
“There is no simple correspondence between an adaptive behavior and any single peptide” and “ there is no necessary unitary relation between a limbic peptide and a single pattern of behavior” (Herbert, 1993). These statements were applied on a wide range of neuropeptides, including oxytocin (OT), and remain just as true as they were about two decades ago. Despite our considerably increased knowledge about locations and mechanisms of OT-release, the physiological and behavioral effects of OT on reproductive behavior in mammals (including humans) remain a complex matter of “whispered secrets and public announcements” (Leng and Ludwig, 2008).
Oxytocin (OT) is a nonapeptide with a molecular weight of 1007 Da, isolated and characterized in 1953 (Du Vigneaud et al., 1953). OT is produced in magno- and parvocellular neurons of the paraventricular hypothalamic nucleus (PVH), in the supraoptic hypothalamic nucleus (SON) as well as in accessory hypothalamic neurons, located in between these nuclei as well as in the bed nucleus of the stria terminalis (BNST) and medial preoptic area (MPOA) and mostly surrounding hypothalamic blood vessels (Armstrong and Hatton, 1980, Armstrong et al., 1980, Bealer et al., 2010, Kelly and Swanson, 1980, Sawchenko and Swanson, 1982b, Swanson, 1987, Swanson and McKellar, 1979a). The magnocellular neurons of PVH and SON send their fibers to the posterior pituitary, where the content is released in the vasculature to enter the general circulation to get access to all receptive peripheral organs (Bargmann, 1949, Kelly and Swanson, 1980, Swanson, 1987). The magnocellular projections form the hypothalamo-neurohypophysial tract, which bends laterally and ventrally around the fornix and ventromedial hypothalamic nucleus (VMH) before entering the internal lamina of the median eminence. The PVH, the SON and the accessory groups each contribute about one third of the fibers entering the posterior pituitary (Rhodes et al., 1981, Swanson, 1987). In addition to the pituitary-directed projections, the PVH projects to target areas within the central nervous system (CNS). It was long thought that these projections originated exclusively from parvocellular OT-neurons located in the dorsal PVH, however, some recent studies showed that magnocellular OT-neurons project to CNS-target areas as well (Knobloch et al., 2012, Ross et al., 2009, Ross and Young, 2009). The destinations of central OT-projections vary from the olfactory bulbs to the lumbosacral spinal cord and involves numerous limbic and brainstem regions (Buijs, 1978b, Buijs et al., 1978, Knobloch et al., 2012, Ono et al., 1978, Ross et al., 2009, Ross and Young, 2009, Sawchenko and Swanson, 1982b, Swanson and McKellar, 1979a, Yu et al., 1996b).
Concerning the functional aspects of the OT-neurons in PVH and SON, many studies have shown their involvement in a variety of physiological and behavioral functions. A major challenge in this field of research is the difficulty to manipulate central oxytocin neurotransmission, since both OT and the currently available OT-receptor antagonists do not readily cross the blood–brain barrier. A currently ongoing debate centers around the question as to whether peripherally or intranasally administered OT can affect central neurotransmission and thereby influence behavior. Recent studies and reviews have come to an affirmative conclusion and intranasally administered OT is currently applied in humans for the treatment of mental illness (Churchland and Winkielman, 2012; Kagerbauer et al., 2013; Neumann et al., 2013; Veening and Olivier, 2013).
Originally most applications for humans were in the clinical realm, in the form of treatments induce uterine contractions during labor or the milk flow in the lactation period, frequently by intranasal administration (Hendricks and Gabel, 1960, Huntingford, 1961). Later on OT was also applied for the treatment of other diseases and over the last decade the effects of OT in social interactions in humans (‘mind-reading’, trust, ‘face-processing’, autism and fear-reduction) are being extensively explored (Behnia et al., 2014, Koch et al., 2014), see (Veening and Olivier, 2013) for a recent review. In animal experiments the effects of OT on social and affiliative behavior were also evident (Insel, 1992) as were the effects on parental behavior, food intake, grooming behavior and pain relief (Lee et al., 2009, Neumann and Landgraf, 2012, Veening et al., 2010, Veening and Olivier, 2013). The behavioral effects of OT are ‘prosocial’ (Lukas et al., 2011, Shelley et al., 2006) and are not typical for humans and rodents, since similar ‘nonapeptide-effects’ have been observed in a variety of other species, from mollusks via teleosts and birds to primates, including man (Churchland and Winkielman, 2012, Insel, 2010, Knobloch and Grinevich, 2014, Snowdon et al., 2010).
From the obvious ‘prosocial’ effects of OT it is not a major step to study the effects of OT on male and female social behavior. A remarkable effect of OT was observed in voles and other rodents where monogamously living species were clearly different from the polygamous species in the density and distribution of OT-fibers and -receptors (Carter, 2014, Carter et al., 1995, Carter and Porges, 2013, Gimpl and Fahrenholz, 2001, Insel, 2010, Insel and Shapiro, 1992, Knobloch and Grinevich, 2014, Lee et al., 2009, Manning et al., 2012, Neumann, 2008, Neumann and Landgraf, 2012, Pedersen and Tomaszycki, 2012, Veenema and Neumann, 2008, Weisman et al., 2012, Witt et al., 1990, Young et al., 2005).
In our present review we will present an overview of the known effects of OT on male and female reproductive behavior. Concerning the physiological and pharmacological details of the neuronal circuitry, a large amount of additional information has become available over the last decades but many questions remain to be answered. For some recent reviews, see (Snoeren et al., 2013a, Snoeren et al., 2013b, Veening and Coolen, 2013, Veening et al., 2013).
Section snippets
Getting together: role of OT in pair bonding
In monogamous pairs, either ‘romantic’ human couples (Borrow and Cameron, 2012, Carter, 2014, Carter and Porges, 2013, Grewen et al., 2005, Light et al., 2005) or long-term attached pairs of rodents like prairie voles (Cho et al., 1999, Williams et al., 1992a, Williams et al., 1992b), the affiliative effects of OT have been extensively documented (Carter, 2014, Carter et al., 1995, Insel, 2010, Insel and Shapiro, 1992, Lukas et al., 2011, Neumann, 2008, Ross et al., 2009, Snowdon et al., 2010,
Doing the deed: role of OT in female sexual behavior
Whereas the level of pair-bonding and affiliate behavior varies widely among mammalian species (and the associated neuroanatomy and dynamics of the OT system as well), male and female sexual behavior is much more stereotyped. Although the temporal pattern of copulation differs between species and even within rodent species (for example, rats are much faster to initiate and complete copulation than mice), all mammals display a similar list of sexual behaviors (for example mounts and
The fruits of labor: role of OT in parental care
The crucial role of OT in various physiological and behavioral aspects of the peri-partum period is well known. Most knowledge has been derived from female mammals, in particular rats and mice, but more recently other species have been investigated as well. There is an increasing interest in mammalian species in which the male plays a substantial role in the care for offspring. The role of OT in paternal behavior is therefore highlighted in this review.
The VMHvl: a puzzling brain region ...!
In the experiments of Cameron et al. (Cameron et al., 2011) it was observed that the less receptive high-LG females showed the greatest neural activation in the VMHvl after mating. Since less than 50% of the activated neurons show ERα-immunoreactivity (Calizo and Flanagan-Cato, 2003, Tetel et al., 1994a, Tetel et al., 1993, Tetel et al., 1994b), it is possible that some of the mechanisms working in the area lateral to the VMHvl do not promote lordosis, but prepare the female for the termination
Summary and conclusions
The conclusion seems warranted that under normal circumstances OT plays an important facilitating role during both male and female reproductive behavior, in rodents (Pedersen and Boccia, 2002) and other mammals including man and the ‘unifying principle’ of the OT action in the brain “is to facilitate social encounters by reducing the associated anxiety” (McCarthy, 1995). Much research is needed to further delineate the complex organization of the neural networks involved in reproductive and
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