Behavioral stress decreases plasma oxytocin concentrations in primates

Using rhesus monkeys, we studied the effects of a behavioral stress on plasma concentrations of adrenocorticotropin, oxytocin, and vasopressin. The stress resulted in significant increases in adrenocorticotropin and significant decreases in oxytocin concentrations. No significant changes were seen in vasopressin concentrations. To further explore the relationship between plasma oxytocin and pituitary-adrenal function, dexamethasone was administered to rhesus monkeys. This resulted in significant increases in plasma oxytocin concentrations, while adrenocorticotropin decreased.     

Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys.

Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.     

Simple method for assaying serum oxytocin and changes of serum oxytocin level during parturition in cynomolgus monkeys.

A novel and simple assay system using a 96-well ELISA plate was established for measuring serum oxytocin in cynomolgus monkeys. This method omits the centrifuge for B/F separation because the second anti-rabbit IgG antibody-coated ELISA plate can easily separate the first anti-oxytocin rabbit antibody-bound radiolabeled oxytocin. Since this method has the advantage of omitting B/F separation, it becomes possible to measure a large number of samples with simple steps. In addition, accurate and reproducible results could be obtained by this method. The optimal reaction condition made it possible to measure more than 8 pg/ml of serum oxytocin. The changes of serum oxytocin level in relation to the first delivery was determined in a total of 11 female monkeys who were divided into two groups, infant-accepting mothers (4 monkeys) and infant-rejecting ones (7 monkeys). The serum oxytocin levels of pre-delivery (one to 4 days before delivery) and post-delivery (within 12 hr after delivery) in infant-accepting mothers were 33.6 +/- 4.57 and 43.5 +/- 16.4 pg/ml, respectively. Those in infant-rejecting mothers were 39.0 +/- 9.6 and 31.4 +/- 7.0 pg/ml. Two-way ANOVA (accepting/rejecting x pre/post) revealed a significant interaction of two factors (F (1, 9) = 5.39, p < 0.05). This result implies the possibility of a different pattern of oxytocin secretion between infant-accepting and infant-rejecting mothers during parturition.     

Reconciliation following aggression in patas monkeys,Erythrocebus patas

Following intra-group aggression, obvious conciliatory displays are absent from the behavioural repertoire of patas monkeys, Erythrocebus patas, while many other Old World primate species show special reconciliation gestures. When 10-min focal-animal samples that began after spontaneous aggression were compared with matched-control samples, captive adult female patas followed up on aggressive interactions, interacting sooner and more often with former opponents during post-conflict observations than during matched-control observations. Almost one-third of post-conflict observations included affiliative behaviour between former opponents, which is termed reconciliation. Matrilineally related opponents were more likely to reconcile with one another than were unrelated animals. No effect of the dominance hierarchy on tendency to reconcile was found. Thus, patas monkeys showed general patterns in post-conflict behaviour that were similar to those seen in other primates previously investigated.     

Participation of pentagastrin and oxytocin in organizing neural activity of the dorsal hippocampus during result- and conflict-oriented feeding behavior in rabbits

Single unit activity of CA3 dorsal hippocamp has been registered in free moving rabbits. The influence of microiontophoretic application of pentagastrin and oxytocin on neuronal involvement into feeding or defensive behaviour has been studied. The change of the dominant feeding motivation to defensive was shown to cause resettings in the typical feeding activity of most neurons. Microiontophoretic application of pentagastrin induces typical feeding activity even if rabbits demonstrate defensive behaviour. It is believed that pentagastrin presence in perineuronal area leads to the involvement of most hippocampal neurons into the organization of the feeding behaviour.     

A social developmental study of young monkeys (Callithrix jacchus) within a captive family group

Quantitative data were collected on the behaviour of one captive family group of common marmoset monkeys over some six months, which included a period immediately before the birth of a third set of twins, and up to the birth of the fourth set. Data were consistently collected on marking, auto and social grooming, as well as on three general categories of play behaviour. In addition, observations were recorded on the carrying of infants by other members of their family, until the end of the fourth week after the birth. The study demonstrated quantitative changes in the behaviour of juvenile and adult members of the family, and indicated the time scale of increasing involvement of the youngest monkeys in some of the major patterns of behaviour in the life of a family social unit.     

Studies on the role of oxytocin in late pregnancy in the pregnant rhesus monkey: plasma concentrations of oxytocin in the maternal circulation throughout the 24-h day and the effect of the synthetic oxytocin antagonist [1-beta-Mpa(beta-(CH2)5)1,(Me(Tyr2, Orn8] oxytocin on spontaneous nocturnal myometrial contractions

Previous observations have demonstrated that under several different circumstances the pregnant rhesus monkey myometrium shows a spontaneous shift in activity from contractures to contractions around the beginning of the hours of darkness. Preliminary studies were conducted to demonstrate that the competitive oxytocin antagonist ([1-beta-Mpa(beta-(CH2)5)1,) Me)Tyr2, Orn8] oxytocin was effective in vivo in inhibiting oxytocin induced contraction type myometrial activity in the pregnant rhesus monkey in the last third of gestation. Four pregnant and one fetectomized rhesus monkey (98-141 days gestation) received one intra-arterial dose of oxytocin antagonist to study its ability to inhibit myometrial contractions occurring spontaneously around the onset of prevailing nighttime. In three pregnant monkeys (105-121 days gestation) maternal arterial plasma oxytocin levels were measured at 4-h intervals for a period of 48 h. Maternal plasma oxytocin concentration was maximal during the early hours of darkness and demonstrated a significant 24-h rhythm. From the combined results of both experiments it may be concluded that circulating oxytocin and/or a change in one of the many potential regulatory sites for oxytocin function plays a role in the switch from contractures to contractions that occurs around the beginning of the hours of darkness.     

Effect of naloxone administration upon the diurnal concentrations of oxytocin in the cerebrospinal fluid of rhesus and cynomolgus monkeys.

A diurnal pattern in oxytocin concentrations is present in cerebrospinal fluid (CSF) removed from the spinal subarachnoid space of monkeys, with elevated levels occurring in the early light hours. In order to investigate the possible role of endogenous opioid peptides in the generation of this oxytocin rhythm, we administered naloxone (0.4 mg/kg/h x 48 h) to rhesus and cynomolgus monkeys and examined the effects on the diurnal pattern of oxytocin in CSF collected from the lumbar subarachnoid spinal space. Monkeys maintained on jacket/tether/swivel systems and in a 12 h light: 12 h dark cycle (lights on 07.00-19.00 h) were implanted with temporary spinal subarachnoid catheters. CSF was continuously collected from the lumbar subarachnoid space and assayed for oxytocin. Oxytocin concentrations in CSF showed a diurnal variation with peak and nadir concentrations during light and dark hours, respectively. The lumbar CSF concentrations of oxytocin were not significantly different during naloxone vs. saline infusion. Plasma oxytocin concentrations, measured in the same animals, displayed no diurnal variation and were not significantly different during naloxone vs. saline infusion. We conclude that naloxone administration for 48 h does not perturb the diurnal variation in oxytocin concentrations in the CSF of monkeys. Mu opioid receptors are unlikely to be involved in modulating the diurnal rhythm of oxytocin in the CSF of monkeys.     

The influence of day-night cycles and the additive effects of methamphetamine and illumination on the spontaneous activity in rhesus monkeys (Macaca mulatta)

The spontaneous activity of rhesus monkeys in a cage situation was measured under 12 hr. day-night cycles in Exp. I. Without exception, all the subjects (n=10) proved to be more active in the daytime than at night. In Exp. II the effect of methamphetamine upon spontaneous activity was investigated in light and dark conditions. It is supposed in the present study that methamphetamine and illumination raise the arousal level of the subjects and increase their spontaneous activity. The results show that the spontaneous activity of rhesus monkeys, which are thought to be visually dominant, greatly depends on illumination. That is, rhesus monkeys move around well in light conditions but little in dark conditions. Methamphetamine increases spontaneous activity, however, in dark as well as in light conditions. Interaction between methamphetamine and illumination effects was not significant. It would appear from these results that both internal and external factors—methamphetamine and illumination—feed into a common pool of the arousal level which controls spontaneous activity.     

The Involvement of Oxytocin in the Subthalamic Nucleus on Relapse to Methamphetamine-Seeking Behaviour

The psychostimulant methamphetamine (METH) is an addictive drug of abuse. The neuropeptide oxytocin has been shown to modulate METH-related reward and METH-seeking behaviour. Recent findings implicated the subthalamic nucleus (STh) as a key brain region in oxytocin modulation of METH-induced reward. However, it is unclear if oxytocin acts in this region to attenuate relapse to METH-seeking behaviour, and if this action is through the oxytocin receptor. We aimed to determine whether oxytocin pretreatment administered into the STh would reduce reinstatement to METH use in rats experienced at METH self-administration, and if this could be reversed by the co-administration of the oxytocin receptor antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae into the STh under isoflourane anaesthesia. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour sessions under a fixed ratio 1 schedule for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.2 pmol, 0.6 pmol, 1.8 pmol, 3.6 pmol) or co-administration of oxytocin (3.6 pmol) and desGly-NH₂,d(CH₂)₅[D-Tyr²,Thr⁴]OVT (3 nmol) into the STh (200 nl/side) was examined on METH-primed reinstatement (1 mg/kg; i.p.). We found that local administration of the highest oxytocin dose (3.6 pmol) into the STh decreased METH-induced reinstatement and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT had a non-specific effect on lever press activity. These findings highlight that oxytocin modulation of the STh is an important modulator of relapse to METH abuse.     

The pineal and oxytocin synthesis.

The aim of this study was to investigate the effect of pineal removal on oxytocin synthesis in the hypothalamus using the colchicine method. To this end, rats were injected intracerebroventricularly (i.c.v.) with colchicine solution (5 microg/5 microl) or normal saline and decapitated 20 h later. The animals were either pinealectomized or sham-operated two or eight weeks before i.c.v. injection. The oxytocin content in the hypothalamus was significantly higher in colchicine-treated rats whereas no significant differences were seen in the neurohypophysial hormone level between saline- or colchicine-injected animals. Thus, colchicine inhibited the hormonal transport but probably did not affect the function of the neurohypophysis. Two weeks after pinealectomy neither the oxytocin synthesis rate nor its neurohypophysial content were significantly different from control values. The oxytocin synthesis rate was increased markedly eight weeks after pineal removal. At that time, the neurohypophysial oxytocin content was reduced suggesting the increased secretion of the hormone. It is concluded that the pineal has an inhibitory impact on both oxytocin synthesis and release.     

Biphasic effect of a prostacyclin methyl ester analog on uterine contractility in the chronically catheterized pregnant rhesus monkey in late gestation

We determined the in vivo effects of a prostacyclin methyl ester analog (PGI2) administration on myometrial activity in twelve chronically- catheterized pregnant rhesus monkeys during the last third of pregnancy under three different states of myometrial contractility: postsurgical contractions, spontaneous contractures and oxytocin induced contractions. Prostacyclin (200 micrograms) was administered to four monkeys 2-3 h after surgery, to eight monkeys having only contractures, and to four monkeys having oxytocin induced contractions. Vehicle administration was performed in six animals having contractures and to four having oxytocin induced contractions. In all three experimental paradigms PGI2 administration elicited a biphasic response in uterine contractility. An initial increase in the 5 min average intrauterine pressure (IUP) value from 2.3 +/- 1.29 to 5.8 +/- 2.29; 3.6 +/- 2.38 to 7.6 +/- 3.59; and 2.3 +/- 0.65 to 8.6 +/- 0.72 (SD); was observed in the post-surgical, spontaneous contracture and oxytocin induced contraction groups respectively (mmHg, P less than 0.05). This increase was followed by a fall in the 5 min average IUP from 2.3 +/- 1.29 to 0.6 +/- 0.49; 3.6 +/- 2.38 to 1.3 +/- 0.86; and 2.3 +/- 0.65 to 0.1 +/- 0.11 in the post-surgical, spontaneous contracture and oxytocin induced contraction groups respectively (mmHg, P less than 0.05). A fall in mean arterial blood pressure from 89 +/- 9.0 to 55 +/- 10.9 (mmHg, P less than 0.05) and a compensatory tachycardia from 108 +/- 18.2 to 164 +/- 56.2 (beats.min-1, P less than 0.05) was observed by 10 min after PGI2 administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental grounds for the effectiveness of ciprofloxacin and oxytocin combined use

In order to determine the influence of combined use of ciprofloxacin and oxytocin on susceptibility of microflora to antibiotics as well as level of microbial anti-lysozyme (ALA) and anti-complement activity (ACA) 148 anaerobic and aerobic microorganisms were isolated from 80 patients with purulent infections of soft tissues. Susceptibility of staphylococci, streptococci, and enterobacteria to the most commonly used antibiotics was assessed by agar-diffusion method with standard disks. ALA and ACA of the isolated strains were defined by routine methods. Minimal inhibitory concentration (MIC) of ciprofloxacin and oxytocin for isolated pathogens were determined according to standards of NCCLS. Influence of oxytocin on MIC of ciprofloxacin was determined as well as inhibitory effect of the latter on factors of bacterial persistence. Decrease of MIC of ciprofloxacin as well as increase of its inhibitory effect on pathogens' ALA and ACA when it used in combination with oxytocin were noted. Usefulness of combined use of ciprofloxacin and oxytocin for treatment of different infections has been proposed.     

Self-wrist biting in Arashiyama-B troop of Japanese monkeys (Macaca fuscata fuscata)

Self-wrist biting in the Arashiyama-B troop of Japanese monkeys was observed during a nearly 4-year study. In all, six monkeys were seen performing this behavioural pattern. Medium ranking monkeys belonging to the age class 2–7 years performed this behavioural pattern most frequently. A slight tendency for the diffusion of this behaviour along kinship lines was also observed.     

Effect of femtomolar concentrations of hormones on insulin binding by Tetrahymena, as a function of time

The unicellular ciliate Tetrahymena, contains and binds hormones, characteristic of vertebrates. Earlier experiments demonstrated the effect of extremely low concentrations of hormones. In the present experiments, the effect of various hormones (endorphin, serotonin, histamine, insulin and epidermal growth factor [EGF]) in 10(-15) M, or oxytocin, gonadotropin at 0.001 IU concentrations) on the binding of FITC-insulin was studied by using flow cytometry and confocal microscopy, after 1, 5, 15, 30 and 60 min. Six of the seven hormones promptly decreased the cells' hormone binding capacity, the exception being EGF, and in four cases (endorphin, serotonin, insulin and oxytocin) the reduction was enormous. The decreased binding was durable. However, in the case of endorphin and oxytocin after 30 min, and in the case of serotonin after 60 min the binding returned to the control level. In the case of oxytocin after 60 min, binding significantly surpassed the control level. Histamine returned to the control level after 15 min, but after that the binding became even lower. EGF provoked special behaviour: it increased hormone binding after 30 and 60 min. The results call attention to the extreme sensitivity of Tetrahymena receptors to hormonal inductions and to its quick response ability.     

Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys

Relatively little is known about serotonergic involvement in pair-bonding despite its putative role in regulating social behavior. Here we sought to determine if pharmacological elevation of serotonin 1A (5-HT_1A) receptor activity would lead to changes in social behavior in pair-bonded male titi monkeys (Callicebus cupreus). Adult males in established heterosexual pairs were injected daily with the selective 5-HT_1A agonist 8-OH-DPAT or saline for 15 days using a within-subjects design. Social behavior with the female pair-mate was quantified, and plasma concentrations of oxytocin, vasopressin, and cortisol were measured. When treated with saline, subjects showed reduced plasma oxytocin concentrations, while 8-OH-DPAT treatment buffered this decrease. Treatment with 8-OH-DPAT also led to decreased plasma cortisol 15 minutes post-injection and decreased social behavior directed toward the pair-mate including approaching, initiating contact, lipsmacking, and grooming. The reduction in affiliative behavior seen with increased activity at 5-HT_1A receptors indicates a substantial role of serotonin activity in the expression of social behavior. In addition, results indicate that the effects of 5-HT_1A agonism on social behavior in adulthood differ between rodents and primates.     

Spinal effects of oxytocin on uterine motility in anesthetized rats

The rat uterus receives an innervation from the lumbosacral and thoracolumbar segments of the spinal cord. These segments receive descending oxytocinergic projections from the paraventricular nucleus of the hypothalamus. We tested the hypothesis that oxytocin regulates uterine motility through a spinal site of action. Oxytocin was administered in anesthetized female rats either intrathecally at the lumbosacral or thoracolumbar spinal cord levels or intravenously. Uterine activity was revealed by measuring changes of intrauterine pressure using an indwelling balloon placed in one caudal uterine horn. The uterus displayed a spontaneous activity characterized by intrauterine pressure rises, the frequency, amplitude, and duration of which were dependent on the stage of the estrous cycle. Oxytocin delivered at the lumbosacral level affected the frequency (during proestrus, estrus, and diestrus) and amplitude (during proestrus and estrus) of uterine activity. During estrus, oxytocin delivered at the thoracolumbar level affected the frequency, amplitude, and duration of the intrauterine pressure rises. Intravenous oxytocin not only affected intrauterine pressure rises (namely amplitude during proestrus and estrus and frequency and duration during estrus) but also increased the basal tone during estrus. The effects of lumbosacral oxytocin were partly mimicked by the oxytocin agonist [Thr(4),Gly(7)]-oxytocin blocked by the oxytocin receptor antagonist atosiban and by hexamethonium. Arginine vasopressin delivered at the lumbosacral level had no effect. These results support our hypothesis that oxytocin released by descending paraventriculo-spinal pathways and acting on spinal oxytocin receptors modulates the activity of the uterus. This regulation is cycle dependent.     

Differences in the effects of vasopressin and oxytocin on rabbit myometrial activity and a possible mediation of prostaglandins

Uterine responses to vasopressin and oxytocin were monitored in non-pregnant and 3- or 6-8-day-pregnant rabbits by recording the intrauterine pressure. Oxytocin stimulated uterine activity in all groups, but the effect of vasopressin was stimulatory in non-pregnant animals, inhibitory in those 3 days post coitum and weakly stimulatory in those later in pregnancy. Inhibition of prostaglandin (PG) synthesis, by the administration of indomethacin, reduced the spontaneous uterine activity as well as the responses to oxytocin and vasopressin in the non-pregnant rabbits, but had little effect in the pregnant animals. During infusion of PGF-2alpha, PGE-1 or PGE-2 in 6-8-day-pregnant rabbits, the stimulatory response to vasopressin, although slight before the infusion, was inhibited whereas the stimulatory response to oxytocin remained virtually unchanged. The results suggest that vasopressin and oxytocin under certain hormonal conditions, are able to activated the uterine contractions by mechanisms in which the involvement of PG is not obligatory.     

Effect of oxytocin on the activity of posterior hypothalamic neurons in the rat

Changes of unit activity in different nuclei of the posterior hypothalamus induced by intravenous oxytocin injections were studied in acute experiments on Wistar rats anaesthetized with nembutal. Influence of nonapeptide was dose-dependent. Latencies of various neuronal reactions were different. Mechanisms of oxytocin regulation of neuronal activity in the posterior hypothalamus are discussed.     

The effect of oxytocin on human-directed social behaviour in dogs (Canis familiaris)

The oxytocin system has recently received increasing attention due to its effect on complex human behaviours. In parallel to this, over the past couple of decades, the human-analogue social behaviour of dogs has been intensively studied. Combining these two lines of research (e.g. studying the relationship between dog social behaviour and the oxytocin system) is a promising new research area. The present paper reviews the existing literature on how oxytocin is related to different aspects of human-directed social behaviour in dogs.