The role of central oxytocin in obsessive compulsive disorder and related normal behavior.

Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the CNS as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. Obsessive Compulsive Disorder (OCD) includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with OT. Anecdotal data and a recently completed cerebrospinal fluid (CSF) study provide evidence that some forms of OCD are related to OT dysfunction. Based on these findings, we hypothesize: 1) that some forms of OCD are at the extreme end of a range of normal behaviors that are mediated by OT and related systems; and that 2) some normal cognitive, affiliative, and sexual behaviors contain elements that are similar to features of OCD. Alternative hypotheses are considered, and a series of predictions are presented concerning the relationship between central OT and the onset, course, treatment response, and response to challenge procedures seen in this form of OCD.

Biosynthesis of vasopressin by gastrointestinal cells of Brattleboro and Long-Evans rats.

The distribution of vasopressin, provasopressin, vasopressin-associated neurophysin, and vasopressin-associated glycopeptide was determined immunohistochemically in the gastrointestinal system of Brattleboro and Long-Evans rats. Cells containing immunoreactivity for vasopressin, provasopressin, neurophysin, and glycopeptide were detected in the same cell types of the stomach and duodenum, while selected cells in the duodenum contained only immunoreactive glycopeptide. Unlike that in the hypothalamus, staining for neurophysin in the gastrointestinal tract was sensitive to fixation. These findings indicate that vasopressin is produced by cells in the rat gastrointestinal system and suggest the existence of synthetic pathways different from those found in hypothalamic neurons.

Absence of negative feedback by oxytocin on release from magnocellular neurones in conscious rats.

Peripheral administration of vasopressin (VP) was previously shown to exert a negative feedback influence on its own release and on the release of oxytocin (OT). In this study we examined the possible influence that OT has on the function of hypothalamic magnocellular neurones. Oxytocin was administered intraperitoneally and its effects on release from VP neurones and from OT neurones were determined as indexed by plasma concentrations of vasopressin-associated neurophysin ([VP-RNP]) and oxytocin-associated neurophysin ([OT-RNP]) under basal conditions and conditions of high plasma osmolality (Posm) induced by acute salt loading. Studies were performed on conscious, chronically instrumented Long-Evans rats. Oxytocin (1 nmol or 10 nmol) dissolved in 1 mL of 0.9% saline was administered intraperitoneally to animals 1 h before they received an intravenous infusion of hypertonic saline over 60 min at a rate designed to raise Posm by approximately 0.75 mosmol.min-1. Intraperitoneal injection of vehicle or 1 nmol of OT did not significantly alter [VP-RNP], [OT-RNP], or basal Posm. Administration of 10 nmol OT also had no effect on [VP-RNP] or [OT-RNP], but this dose of peptide significantly lowered basal Posm (299 +/- 2 to 290 +/- 2 mosmol/kg H2O, p less than 0.001). Both doses of OT did not significantly alter the responsiveness of VP neurones to hyperosmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Putative precursors of vasopressin, oxytocin, and neurophysins in the rat hypothalamus.

The biosynthesis of [arginine8]vasopressin (AVP) and oxytocin (OT) was studied, and the results obtained have been compared with a study of their associated neurophysins (NP), AVP-NP and OT-NP. Rat hypothalamic extracts obtained at acid pH were subjected to Sephadex G-75 gel filtration chromatography and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE). Fractions of gel chromatography effluent and extract of SDS-PAGE gel slices were subjected to RIA for immunoreactive precursors of AVP, AVP-NP, OT, and OT-NP using specific antisera fro each molecule. Tritiated bovine serum albumin, ovalbumin, and cytochrome c were used as internal standards during gel filtration chromatography and SDS-PAGE. Molecular weight estimates obtained for precursors of AVP were more than 70K, 31K, 13K, 5K, and less than 5K (AVP) by G-75 chromatography and more than 70K, 39K, 15K, and less than 5K (AVP) by SDS-PAGE. Molecular weight estimates obtained for precursors of AVP-NP were more than 70K, 35K, 24K, and 12K (AVP-NP) by G-75 chromatography and 19K and 10K (AVP-NP) by SDS-PAGE. Molecular weight estimates of OT were more than 70K, 35K, 19K, 8K, and less than 5K (OT) by G-75 chromatography and 60K, 35K, 19K, 9K, and less than 5K (OT) by SDS-PAGE. Precursors of OT-NP were estimated to be more than 70K, 17-18K, and 10K (OT-NP) by G-75 chromatography and 28K, 18K and 10K (Ot-NP) by SDS-PAGE. These studies show that there are small differences in precursor processing among AVP, AVP-NP, and OT, OT-NP, but allow for the existence of common precursors for AVP and AVP-NP and for OT and OT-NP.

The pharmacology of a new oxytocic principle from ox hypothalamus.

1. An oxytocic substance has been isolated from ox hypothalamus by successive gel filtration on Sephadex G-25 and Sephadex G-50, and its pharmacology has been examined on three smooth muscle preparations.2. The substance has the same order of potency on rat uterus, guinea-pig ileum, and hen rectal caecum.3. The action of the substance on rat uterus was not abolished by thioglycollate.4. Atropine (1.0 mug/ml.), phenoxybenzamine (0.1 mug/ml.) and mepyramine (1.0 mug/ml.) did not block the smooth muscle action of the substance.5. Drug action, relative potency, and log dose-response relationships distinguish the substance from 5-hydroxytryptamine, acetylcholine, oxytocin, vasopressin, angiotensin amide, bradykinin, and purified preparations of substance P.