Nonsocial Functions of Hypothalamic Oxytocin

Abstract

Oxytocin (OXT) is a hypothalamic neuropeptide composed of nine amino acids. The functions of OXT cover a variety of social and nonsocial activity/behaviors. Therapeutic effects of OXT on aberrant social behaviors are attracting more attention, such as social memory, attachment, sexual behavior, maternal behavior, aggression, pair bonding, and trust. The nonsocial behaviors/functions of brain OXT have also received renewed attention, which covers brain development, reproduction, sex, endocrine, immune regulation, learning and memory, pain perception, energy balance, and almost all the functions of peripheral organ systems. Coordinating with brain OXT, locally produced OXT also involves the central and peripheral actions of OXT. Disorders in OXT secretion and functions can cause a series of aberrant social behaviors, such as depression, autism, and schizophrenia as well as disturbance of nonsocial behaviors/functions, such as anorexia, obesity, lactation failure, osteoporosis, diabetes, and carcinogenesis. As more and more OXT functions are identified, it is essential to provide a general view of OXT functions in order to explore the therapeutic potentials of OXT. In this review, we will focus on roles of hypothalamic OXT on central and peripheral nonsocial functions.

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain

“…Expression in the motor nuclei of cranial nerves is also found in rodents (in particular in the X and XIII) (34) and marmosets (V and X) (35), indicating a shared capability of OT to directly and rapidly influence some motor and autonomic responses to social stimuli. 3 Rodents, which primarily use olfactory inputs for social recognition and social memory, present as a common feature a high level of OTR expression in the olfactory system, which is the primary modality of social investigation and interaction. Finally, in primates, OTR are found in the nucleus basalis of Meynert and the superior colliculus in the four primate species analyzed so far [marmoset (35), coppery titi monkey (37), rhesus macaque (29), and human (38)].…”

“…Other areas involved in social behavior depicted here include: medial septum (MS); high vocal center (HVC); robust nucleus of the arcopallium (RA); and motor nucleus of the XII cranial nerve (XII) in panel (B); olfactory bulb (Ob) and anterior olfactory nucleus (AON) in panel (C); nucleus basalis of Meynert (NBM); superior colliculus (SuC); pedunculopontine tegmental nucleus (PPT); and trapezoid body (TB) in panel (D). 3 The origin of OTergic innervation of motor and cranial nerve nuclei is parvocellular OT neurons, which are allocated in specific subnuclei of the PVN (36). We did not expose here these OT neurons because their evolution, ontogenesis, and connectivity are poorly studied.…”

“…These magnocellular neurons were later shown to produce OT and arginine-vasopressin (AVP) (or their homologs) in two neuron populations found in representatives of all classes of vertebrates. OT and AVP are transported to the posterior pituitary lobe from where they are released into the blood and act on peripheral targets to control water reuptake in the kidney (2) and modulate autonomic functions and metabolism, nociception, analgesia, and immune response (3). During pregnancy and lactation, OT is important for the delivery of newborns in most of mammals, eggs in fish, amphibians, reptiles, and birds, as well as critical for milk ejection.…”

Model Roles of the Hypothalamo-Neurohypophysial System in Neuroscience Study

“…For example, VP is involved in stress, the hypophysialadrenocortical axis, neuroimmune responses, renal function and corticotroph pituitary tumors [124]. Similarly, OXT is extensively involved in many body functions such as sexual activity, penile erection, ejaculation, pregnancy, uterus contraction, milk ejection, maternal behavior, osteoporosis, diabetes, cancer, social bonding, and stress among many others [125,126]. Thus, OXT and its receptor have been considered as potential targets for drug therapy of diseases in the brain and peripheral organs [127].…”

Up-regulation of oxytocin receptor gene and protein in the sheep anterior pituitary by a dopamine derivative (salsolinol)

“…Although most of OT neurons project into the posterior pituitary, where the neurohormone is stored and released into the circulation, OT also reaches the anterior pituitary through the short portal vessels connecting these two parts (Gibbs 1984;Samson and Schell 1995). Additionally, magnocellular oxytocinergic neurons innervate the median eminence, where they can act on the anterior pituitary (Yang et al 2013). OTR immunoreactivity was found in the rat AP (Adan et al 1995), and early studies showed that most OTR are present in lactotrophic cells (Breton et al 1995) where OT plays an important role in stimulating PRL secretion (Samson et al 1986).…”