104 Oxytocin, Arginine Vasopressin and Autism Spectrum Disorder
paraventricular nuclei are completely formed at 25 weeks of gestation and oxy-
tocin‐immunoreactivity is first detected at 26 weeks of age. At that time, the
number of stained oxytocin neurons is relatively similar in the fetal and adult
hypothalamus [10], while the morphologic analysis of individual magnocellu-
lar neurons suggests that these cells are still immature, as indicated by the
subsequent increase of their nuclear volume.
A single oxytocin receptor and vasopressin receptor subtypes (V1α and V1β)
are centrally expressed and distributed widely throughout the brain. Centrally,
particularly high expressions of these receptors are found in regions underly-
ing the control of many social behaviors, such as the nucleus accumbens, ven-
tral tegmental area, amygdala, and hippocampus [10] (Figure 4.3). Although
oxytocin and vasopressin exert a range of neuropeptide specific physiological
functions, there is evidence that they may cross‐react at receptor levels, given
similarities in structure, suggesting that increased activity of one peptide may
also exert some influence over expressivity of the other [67–72].
Along with oxytocin, in males, AVP is also produced in the amygdala and
the bed nucleus of the stria terminalis, transported to the pituitary and
then released into the blood stream where they deliver hormone effects to
tissues. Oxytocin and AVP also can also diffuse into the central nervous
system [1–3,62–79]. The genes for these two neuropeptides are closely
linked on chromosome 20p13, separated by only 12 kb, which allows inter-
action [5,27,46,48].
These neuropeptide hormones have receptors in various brain regions and
throughout the body, including areas that are important for regulating social
behavior and reactivity to stressors (Figure 4.4).
As in humans, the transcriptomic analysis of oxytocin receptor revealed a
progressive increase in oxytocin receptor mRNA during embryonic life in five
out of six brain areas analyzed [73–75]. Remarkably, the receptor level appeared
to reach a maximum prior to birth and remained quite stable thereafter, at least
for the first 5 years of life, although with some individual variations. As we have
shown in Figure 4.2, the human oxytocin receptor area in the brain is fully
mature and ready to respond to oxytocin at birth.Oxytocin and Social Experience in Development
Effects of oxytocin during embryogenesis and neonatal ontogenesis on social
life have been extensively summarized in recent reviews [77,78], but the reverse
effects (i.e., the effects of social stimuli on maturation of the oxytocin system)
have been explored less. It has been reported that early social experience tre-
mendously affects physiology of the oxytocin system [78]. Specifically, it has
been demonstrated that early sensory experience (in the newborn) regulates
development of sensory cortices via oxytocin signaling [63,64].