The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via Gq proteins to phospholipase C-β. The high-affinity receptor state requires both Mg2+ and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has bee...

The Oxytocin Receptor System: Structure, Function, and Regulation

Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications.

Mechanisms of fear extinction

Vasopressin and oxytocin pathways were specifically localized in glutaraldehyde-paraformaldehyde fixed rat brains, with the use of the unlabelled antibody enzyme method and purification of the first antiserum. Vasopressin and oxytocin containing pathways were traced from the paraventricular nucleus towards the dorsal and ventral hippocampus, the nuclei of the amygdala, substantia nigra and substantia grisea, nucleus tractus solitarius, nucleus ambiguus and to the substantia gelatinosa of the spinal cord. In addition, a vasopressin containing pathway between the suprachiasmatic nucleus and the lateral habenular nucleus was demonstrated. The possible nature (axons or dendrites) and role of these extrahypothalamic fibres is discussed in relation to water balance, milk ejection and avoidance behaviour.

Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat

THIS REVIEW will deal with the biosynthesis of many of the members of the ACTH/lipotropin (LPH) family of peptides (Fig. 1). Peptides in this family fall into two groups: peptides related to ACTH include α-melanotropin (αMSH) and corticotropin-like intermediate lobe peptide (CLIP); peptides related to βLPH include γLPH, βMSH, and β-endorphin. In several species ACTH and βLPH each contain an identical heptapeptide segment located in the region of the molecule that is responsible for melanotropic bioactivity (1, 2). In this review we have taken a somewhat historical approach, and will therefore begin with a discussion of the biosynthesis of ACTH and the characterization of biosynthetic precursors to ACTH. When this work began, βLPH, γLPH, and βMSH were well-characterized pituitary peptides, but the opioid peptides (and β-endorphin in particular) had not yet been identified (3–5). Studies on the biosynthesis of ACTH were heavily influenced by prior work defining the biosynthetic pathways for insulin and para...

Structure and Biosynthesis of Pro-Adrenocorticotropin/Endorphin and Related Peptides*

Mechanisms of stress: a dynamic overview of hormonal and behavioral homeostasis.

https://dspace.library.uu.nl/bitstream/handle/1874/17130/wied_75_memory.pdf;sequence=1

Memory deficit in rats with hereditary diabetes insipidus.

https://dspace.library.uu.nl/bitstream/handle/1874/16749/bohus_75_behavioral.pdf;sequence=1

Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

The role of limbic vasopressin and oxytocin in social recognition

The effects of the decapeptide ACTH-(1–10) and [D-phe7]-ACTH-(1–10) were tested on the rate of extinction of a pole-jumping avoidance response in rats. ACTH-(1–10) in doses of 20, 50, and 100 µg inhibited extinction of the avoidance response 4 h following subcutaneous administration. [D-phe7]-ACTH-(1–10) in doses of 20, 50, and 100 µg facilitated extinction 4 h after injection. Intracerebral implantation of approximately 10 µg of these ACTH-analogues in the freely moving rat had similar effects on extinction of avoidance response when implanted into the region of the rostral mesencephalon and the caudal diencephalon, at the posterior thalamic level, or in the cerebrospinal fluid. Ineffective sites were the nucleus ventralis thalami, the nucleus anterior medialis thalami, the nucleus reuniens, the globus pallidus, the nucleus accumbens, the fornix, and the hippocampus. The results support the hypothesis that the site of action of ACTH and of ACTH-analogues on extinction of an avoidance response is localized in the central nervous system.

Effects of systemic and intracerebral administration of two opposite acting ACTH-related peptides on extinction of conditioned avoidance behavior.

Publisher Summary This chapter discusses the role of Vasopressin in memory processes. During the last 10 years, evidence has accumulated that peptides from pituitary origin play an important role in acquisition and/or extinction of conditioned avoidance behavior. Administration of pitressin, a crude vasopressin preparation extracted from posterior pituitary tissue, induces resistance to extinction of a shuttlebox avoidance response. The principle present in pitressin responsible for this “long-term” effect seemed to be vasopressin and proof of this assumption was obtained in experiments in which a pole jump avoidance response was studied. The significance of vasopressin for the consolidation of learned behavior is also demonstrated by experiments in rats with hereditary hypothalamic diabetes insipidus (DI) that lack the ability to synthesize vasopressin. It appeared that homozygous DI rats in contrast to heterozygous littermates were unable to retain the passive avoidance response. Administration of vasopressin and vasopressin analogues induces resistance to the extinction of active and passive avoidance behavior.

Tj.B. van Wimersma Greidanus

Papers

Memory deficit in rats with hereditary diabetes insipidus.

Behavioral and endocrine responses of rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain).

The role of limbic vasopressin and oxytocin in social recognition

Effects of systemic and intracerebral administration of two opposite acting ACTH-related peptides on extinction of conditioned avoidance behavior.

The Role of Vasopressin in Memory Processes