Oxytocin and Developmental Neurological Disorders 107the oxytocin receptor positive neurons leads to an impairment of social
behavior, suggesting that a fine tuning of the oxytocin system is necessary
to develop and control social behavior. Other mouse models, in which the
knockout of a specific gene induced a disruption in the oxytocin system
that has been linked to a pathological phenotype, reinforce the role of oxy-
tocin in neurodevelopmental disorders (Table 4.1). Recently, it has been
shown that disruption of the neonatal surge of oxytocin coming from the
mother during delivery results in autistic‐like features in the adults [87].
Together these data suggest that an early postnatal injury or dysfunction of
the oxytocin system has consequences in infant behavior and subsequently
in the adult behavior.
As previously mentioned, in both the human and mouse genomes, oxytocin
and AVP neuropeptide genes are located adjacently on the same chromosome.
Often the blood levels of both hormones are highly correlated [88], suggesting
a coordinated release. This close proximity facilitates coordinated regulation of
social and adaptive behaviors, the hypothalamic–pituitary–adrenal axis (HPA),
and autonomic nervous systems. At times, they may have opposing physiologic
effects, such as in the autonomic nervous system where oxytocin may have
parasympathetic effects while AVP has regulatory effects. However, at high
levels the neuropeptides can be partial opposing effects for their homologous
receptors, which may result in interactions between the AVP and oxytocin
pathways.
Of particular importance in neurodevelopmental disorders is the fact that
oxytocin and AVP can modulate social and repetitive behavior and other
manifestations of anxiety and state regulation [10]. Animal research has gen-
erally associated oxytocin release or exposure with positive sociality, reduced
anxiety, and lower levels of reactivity to stressors. AVP influences anxiety, the
regulation of the hypothalamic–pituitary–adrenal axis (Figure 4.4), and
stress responses. In general, central AVP has stress and anxiety relaxing
effects. However, evidence in rats has shown a dose related effect. For exam-
ple, AVP may relieve anxiety if given in low doses. Oxytocin receptor and
oxytocin regulator knockout mice exhibit decreased social memory, cogni-
tive flexibility, and resistance to change a learned pattern of behavior in clini-
cal studies [10].
Both social deficits and behavioral rigidity were ameliorated by oxytocin
administration [86]. The finding that oxytocin continues to have effects in oxy-
tocin receptor depleted (knockout) mice supports the notion that oxytocin can
influence behavior through other receptors, especially the AVP receptors (e.g.,
AVPR1α and/or AVPR1β). Given the influence of these neuropeptides on brain
regions affecting both social and repetitive behaviors, modulation of oxytocin
and AVP pathways is being explored as a treatment target for disorders, includ-
ing Fragile X syndrome and ASD.