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Many people enjoy sad music, and the appeal for tragedy is widespread among the consumers of film and literature. The underlying mechanisms of such aesthetic experiences are not well understood. We tested whether pleasure induced by sad, unfamiliar instrumental music is explained with a homeostatic or a reward theory, each of which is associated with opposite patterns of changes in the key hormones. Sixty-two women listened to sad music (or nothing) while serum was collected for subsequent measurement of prolactin (PRL) and oxytocin (OT) and stress marker (cortisol and adrenocorticotropic hormone) concentrations. Two groups of participants were recruited on the basis of low and high trait empathy. In the high empathy group, PRL and OT levels were significantly lower with music compared with no music. And compared to the low empathy group, the high empathy individuals reported an increase of positive mood and higher ratings of being moved with music. None of the stress markers showed any changes across the conditions or the groups. These hormonal changes, inconsistent with the homeostatic theory proposed by Huron, exhibit a pattern expected of general reward. Our findings illuminate how unfamiliar and low arousal music may give rise to pleasurable experiences.

Oxytocin (OXT) in the hypothalamus is the biological basis of social recognition, trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an important role in the hypothalamus in the process of OXT release in adult mice. Disruption of Cd38 (Cd38-/-) produced impairment of maternal behavior and male social recognition in mice, similar to the behavior observed in Oxt and OXT receptor (Oxtr) gene knockout (Oxt-/- and Oxtr-/-, respectively) mice. Locomotor activity induced by separation from the dam was higher and the number of ultrasonic vocalization (USV) calls was lower in Cd38-/- than Cd38+/+ pups. These phenotypes seemed to be caused by the high plasma OXT levels during development from neonates to 3-week-old juvenile mice. ADP-ribosyl cyclase activity was markedly lower in the knockout mice from birth, suggesting that weaning for mice is a critical time window of differentiating plasma OXT. Contribution by breastfeeding was an important exogenous source for regulating plasma OXT before weaning by the presence of OXT in milk and the dam's mammary glands. The dissimilarity of Cd38-/- infant behaviour to Oxt-/- or Oxtr-/- mice can be explained partly by this exogenous source of OXT. These results suggest that secretion of OXT into the brain in a CD38-dependent manner may play an important role in the development of social behavior, and mice with OXT signalling deficiency, including Cd38-/-, Oxt -/- and Oxtr-/- mice are good animal models for developmental disorders, such as autism. © 2011 Pharmaceutical Society of Japan.

Synergizing the effect of afferent fibre stimulation with pharmacological interventions is a desirable goal to trigger spinal locomotor activity, especially after injury. Thus, to better understand the mechanisms to optimize this process, we studied the role of the neuropeptide oxytocin (previously shown to stimulate locomotor networks) on network and motoneuron properties using the isolated neonatal rat spinal cord. On motoneurons oxytocin (1 nM–1 μM) generated sporadic bursts with superimposed firing and dose-dependent depolarization. No desensitization was observed despite repeated applications. Tetrodotoxin completely blocked the effects of oxytocin, demonstrating the network origin of the responses. Recording motoneuron pool activity from lumbar ventral roots showed oxytocin mediated depolarization with synchronous bursts, and depression of reflex responses in a stimulus and peptide-concentration dependent fashion. Disinhibited bursting caused by strychnine and bicuculline was accelerated by oxytocin whose action was blocked by the oxytocin antagonist atosiban. Fictive locomotion appeared when subthreshold concentrations of NMDA plus 5HT were coapplied with oxytocin, an effect prevented after 24 h incubation with the inhibitor of 5HT synthesis, PCPA. When fictive locomotion was fully manifested, oxytocin did not change periodicity, although cycle amplitude became smaller. A novel protocol of electrical stimulation based on noisy waveforms and applied to one dorsal root evoked stereotypic fictive locomotion. Whenever the stimulus intensity was subthreshold, low doses of oxytocin triggered fictive locomotion although oxytocin per se did not affect primary afferent depolarization evoked by dorsal root pulses. Among the several functional targets for the action of oxytocin at lumbar spinal cord level, the present results highlight how small concentrations of this peptide could bring spinal networks to threshold for fictive locomotion in combination with other protocols, and delineate the use of oxytocin to strengthen the efficiency of electrical stimulation to activate locomotor circuits.

Oleoylethanolamide (OEA) is a lipid amide produced by enterocytes upon the absorption of dietary fat and participates in the induction of satiety. Through indirect pathways, probably depending on the local activation of peroxisome-proliferator-activated receptor-alpha and involving afferent vagus nerve fibers, OEA signal is transmitted to the brain-stem and the hypothalamus, where it stimulates the release of oxytocin from magnocellular neurons. OEA mechanism might, thus, provide a novel target for the design of therapies controlling appetite.

International audience; This study was done to verify if the lack of increase of milk fat content observed in Alpine dairy goats under once daily milking (ODM) compared to twice daily milking (TDM), results from disturbances of animals and/or milk ejection reflex. In this respect, we determined the milk yield and composition in the same 12 multiparous Alpine dairy goats when they were managed first under TDM (period 1: P1) and then under ODM (period 2: P2). Furthermore, oxytocin (OT) and cortisol (CORT) releases and milk emission kinetic of these goats were measured at morning milking 2 and 4 times in P1 and P2, respectively. ODM compared to TDM, caused 18 and 23% reductions, respectively in daily milk yield and milk fat content without milk protein content modification. Although baseline concentration of blood OT was lower under ODM than TDM management (7.0 pg/mL vs 17.8 +/- 2.0 pg/mL, respectively), ODM did not modify the total amount of OT released during milking (15,484 pg/mL/32 min vs 18,996 +/- 2865.3 pg/mL/32 min, respectively), the peak concentration of OT (57.2 pg/mL vs 73.6 +/- 10.5 pg/mL, respectively) or the time to reach it (3.0 min vs 2.0 +/- 0.5 min, respectively) by comparison to TDM. ODM compared to TDM, never modified the baseline concentrations of CORT (6.1 ng/mL vs 7.1 +/- 1.1 ng/mL. respectively), the total amount of CORT released (11,727 ng/mL/32 min vs 10,073 +/- 1522.2 ng/mL/32 min. respectively), the peak concentrations of CORT (16.1 ng/mL vs 15.1 +/- 2.1 ng/mL, respectively) and the time to reach it (13.1 min vs 11.0 +/- 1.5 min). During ODM, milk flow latency was reduced (-61%) while the mean flow rate was increased (+28%) by comparison to TDM. CDM compared to TDM management, did not modify the maximum flow rate (1.6 L/min vs 1.6 +/- 0.2 L/min, respectively) or the time to reach this maximum (103.0 s vs 95.0 +/- 10.0 s, respectively). The total milking duration at morning milking was not different (250.0 s vs 221.0 +/- 22.0 s, respectively) although the morning milk yield was significantly higher under ODM management (2.63 kg/d vs 1.87 +/- 0.1 kg/d. respectively). This results show that milk emission is improved under ODM management in Alpine goats without inhibition or disturbance of neuro-hypophyseal OT release pattern and lack of activation of the hypothalamic-pituitary-ad renal axis and plasma cortisol increase, disproving our initial hypotheses of a disturbance of animals and/or incomplete milk ejection to explain the low fat content of milk under ODM in this breed. (C) 2009 Elsevier B.V. All rights reserved.

Introduction: Appropriate social behavior is vital for human health and well-being, nevertheless the neurobiological mechanisms which mediate social behavior remain poorly understood. Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) is a street drug which gained widespread use in the 'club' scene, likely due to the typical behavioral effects of MDMA which are described as an increase in empathy and friendliness. These prosocial effects led to MDMA being categorized as a separate drug class called 'entactogens'. In spite of abundant attention in the scientific literature, the mechanism of MDMAs prosocial effects has not been elucidated in humans, although animal research has suggested that the neuropeptide oxytocin may mediate these MDMA effects [1]. Oxytocin has recently received abundant attention for it's role in social behavior and has been suggested to induce prosocial and affiliative behavior in animals as well as in humans [2]. Objective: To investigate the effect of MDMA on oxytocin levels and subjective prosocial feelings in humans. Methods: In a double blind, randomized, crossover, and placebo-controlled study in fifteen healthy volunteers we investigated whether 100mg orally administered MDMA induces oxytocin release in humans. Blood samples for analysis of MDMA and oxytocin concentration were collected repeatedly during the study day. Subjective prosocial effects were assessed using two sub scales of the Bond and Lader (Visual Analogue) Mood Rating Scale (BLMRS) that specifically assess prosocial effects (antagonistic/amicable and withdrawn/gregarious). Statistical evaluation of drug effects (using SPSS 14 for Windows) was performed with a mixed model analysis of variance with drug and time as fixed factors and subject as random factor. Results: Mean MDMA maximal plasma concentrations (Cmax) were 222.7 μg/l (SD = 38.1 μg/l) 105 minutes after drug administration, and showed minimal decline (174.6 μg/l (SD = 40.0 μg/l) 300 minutes after drug administration). Oxytocin concentrations were significantly increased after MDMA administration [F(1,223)=84.5, p

Introduction: Appropriate social behavior is vital for human health and well-being, nevertheless the neurobiological mechanisms which mediate social behavior remain poorly understood. Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) is a street drug which gained widespread use in the 'club' scene, likely due to the typical behavioral effects of MDMA which are described as an increase in empathy and friendliness. These prosocial effects led to MDMA being categorized as a separate drug class called 'entactogens'. In spite of abundant attention in the scientific literature, the mechanism of MDMAs prosocial effects has not been elucidated in humans, although animal research has suggested that the neuropeptide oxytocin may mediate these MDMA effects [1]. Oxytocin has recently received abundant attention for it's role in social behavior and has been suggested to induce prosocial and affiliative behavior in animals as well as in humans [2]. Objective: To investigate the effect of MDMA on oxytocin levels and subjective prosocial feelings in humans. Methods: In a double blind, randomized, crossover, and placebo-controlled study in fifteen healthy volunteers we investigated whether 100mg orally administered MDMA induces oxytocin release in humans. Blood samples for analysis of MDMA and oxytocin concentration were collected repeatedly during the study day. Subjective prosocial effects were assessed using two sub scales of the Bond and Lader (Visual Analogue) Mood Rating Scale (BLMRS) that specifically assess prosocial effects (antagonistic/amicable and withdrawn/gregarious). Statistical evaluation of drug effects (using SPSS 14 for Windows) was performed with a mixed model analysis of variance with drug and time as fixed factors and subject as random factor. Results: Mean MDMA maximal plasma concentrations (Cmax) were 222.7 μg/l (SD = 38.1 μg/l) 105 minutes after drug administration, and showed minimal decline (174.6 μg/l (SD = 40.0 μg/l) 300 minutes after drug administration). Oxytocin concentrations were significantly increased after MDMA administration [F(1,223)=84.5, p

Milk flow parameters at udder and quarter levels were studied in relation to somatic cell count (SCC) and other risk factors for mastitis (bimodality, duration of decline, and duration of overmilking phase). Thirty-eight Holstein cows in their first to sixth lactations were investigated during 10 mo of lactation. Monthly milk samples were collected for SCC during morning milking. Quarter and udder milk flows were recorded daily. A cow was included if one quarter was found to have an SCC higher than 200 x 10(3) cells/mL. A total of 3,262 quarter milk flow curves and 804 udder milk flow curves from 22 cows (6 primiparous and 16 multiparous) were selected and evaluated. Selected data for milk flow profiles in relation to SCC represented 5 consecutive morning milkings around the time of milk sampling (sampling on d 3). A total of 661 milk samples were analyzed. At both the udder and quarter levels milk yield was reduced in groups with increased SCC. Quarters with high SCC (500 x 10(3) cells/mL) had lower peak flow rate and longer overmilking phases compared with quarters with low SCC (200 x 10(3) cells/mL). There was a tendency for a longer duration of the decline phase in quarters with high SCC but no effect was observed at the udder level. There were longer declines in bimodal milk flows at the quarter, but not at the udder, level. Also, quarters with bimodality had longer overmilking phases. The duration of the decline phases at the quarter level influenced all measured parameters except the duration of the increase phase. The quarters with a longer duration of the decline phase (or = 80 s) had greater SCC and peak flow rate but had lower milk yield compared with quarters with a shorter duration of the decline phase (27 s). Duration of the overmilking phase influenced all measured parameters except SCC. We conclude that for good udder health, the duration of the decline phase at the quarter level should be considered for milking parameters and udder preparation before milking.

This study aims to examine influences of specific boar stimuli on uterine activity in estrous sows, by comparing uterine activity in presence of a mature teaser boar and a robot boar with variable stimuli. Nineteen multiparous, cyclic, commercial crossbred sows were used. Intra-luminal uterine pressure was measured using a non-surgical method for 45 min before applying one of four treatments in combination with a back-pressure-test (BPT): (1) robot with olfactory and auditory stimuli (R + O + A) (n = 16), (2) robot with auditory stimuli (R + A) (n = 16), (3) robot without additional stimuli (R) (n = 16), (4) a mature boar (boar) (n = 15). After treatment, measurements continued for 30 min. For each measurement, frequency, mean amplitude and mean duration of uterine contractions were determined. Spontaneous frequency of uterine contractions was 18.6 ± 0.7 h¿1 on average and did not differ between treatments. Frequency of contractions increased significantly for the boar (+5.6 ± 1.3 h¿1; P

Although aging populations tend to have increased prevalence of a diversity of diseases and disabilities, there are substantial numbers of people who, nevertheless, maintain good health into old age. Human studies frequently demonstrate associations between environmental factors, particularly supportive social environments, and positive states of health. Identifying the pathways from protective social environments to reduced disease risk necessitates the use of animal models as a basis of explanation and a source of suggestions for further human research. We present two examples of this kind of cross-talk: (i) the possibility that the success of well-being therapy following pharmacological treatment for depression as a means of preventing recurrent depressive episodes is based on the stimulation of enrichment of dendritic networks in the hippocampus and spine retraction in the basolateral amygdala; (ii) the possibility that the release of intracerebral oxytocin is a mediating factor between persistently supportive social environments and reduced disease in later life, as exemplified by low levels of allostatic load.

The objective of this study was to evaluate the effect of teat cleaning by two rolling brushes on oxytocin (OT) release, milk ejection and milking characteristics during milking in a single stall automatic milking system (AMS). Five treatments B0 (no brushing), B1 (one brushing cycle for 16 s, 4 s per teat), B2, B4 and B6 (two, four and six brushing cycles, respectively) were randomly changed and quarter milk flow curves were recorded. In addition, blood samples were taken from 10 randomly selected cows during milking at 1-min intervals for OT determination in treatments B0, B2, B4 and B6. Basal OT concentrations were similar (2.7 to 3.9 pg/ml) in all treatments. At the start of milking, OT concentration was lower (P

Milking characteristics and udder evacuation in 3 different quarter specific milking routines were evaluated. The findings are based on single quarter milk flow profiles of 10 cows. Each treatment was applied in blocks of 4 subsequent milkings. After the fourth milking of each treatment 10 I.U. oxytocin were i.v. injected to obtain the residual milk. The intramammary pressure was recorded during pre-milking stimulation and after the teat cup removal to study the course of the milk ejection. Quarter specific milking routines avoided an overmilking of single teats, and partially decreased the total machine on-time. In comparison to non-stripping routines, the stripping routines had no benefit on udder evacuation or machine on-time. The milk ejection in single quarters was completely terminated when the milk flow ceased and the teat cups were removed. The degree of udder evacuation was therefore not influenced by the tested quarter specific routines.

During parturition, the basal activity of the hypothalamo-pituitary-adrenal (HPA) axis of Wistar rats is strongly attenuated, whereas the oxytocin system is activated. We investigated the secretory responses of the HPA axis and oxytocin to exposure to a mild emotional stressor (airpuff) comparing virgin female, d 22 pregnant, and parturient rats. Furthermore, as the brain oxytocin system is activated in parturition and oxytocin has been shown to inhibit HPA axis responses in virgin rats, the role of brain oxytocin in the regulation of stress responses during parturition was investigated by intracerebroventricular administration of an oxytocin receptor antagonist before stressor exposure (0.75 micro g/5 micro l). In virgin female rats, exposure to airpuff increased ACTH (2.5 +/- 0.34-fold) and corticosterone (5.1 +/- 2.3-fold) secretion, but in late pregnancy and parturition, the stress-induced increase in ACTH (pregnancy: 1.9 +/- 0.41-fold; parturition: 1.3 +/- 0.13-fold) and corticosterone secretion (parturition: 1.8 +/- 0.40-fold) were strongly attenuated. Oxytocin secretion remained unchanged in response to airpuff in both virgin and parturient rats despite higher overall plasma concentrations in the latter. Oxytocin receptor blockade in the brain elevated basal and stress-induced ACTH secretion in virgin but not pregnant or parturient rats and had no effect on oxytocin secretion either in virgin or parturient rats. We conclude that the reactivity of the HPA axis to external stressors is strongly attenuated during parturition, and this cannot be disinhibited by blocking the receptor-mediated action of brain oxytocin.

Oxytocin (OT) is released in response to tactile teat stimulation and causes alveolar milk ejection. The objective of this study was to evaluate the effect of teat cleaning by two rolling brushes on OT release and milk ejection during milking in a single stall automatic milking system (AMS, Merlin, Lemmer-Fullwood). Forty-eight German Fleckvieh cows were investigated during their voluntary milkings. Five treatments B0 (no brushing), B1 (1 brushing cycle for 16 s, 4 s per teat), B2 (2 brushing cycles), B4 (4 brushing cycles) and B6 (6 brushing cycles) were performed for 2 days each and quarter milk flow was recorded. In addition blood samples were taken from 10 cows during milking at 1-min intervals for OT determination in treatments B0, B2, B4 and B6. Basal OT concentrations were similar (2.7 to 3.8 pg/ml) in all treatments. At the start of milking, OT concentration was lower (P

Introduction: Appropriate social behavior is vital for human health and well-being, nevertheless the neurobiological mechanisms which mediate social behavior remain poorly understood. Ecstasy (3,4-methylenedioxymethamphetamine (MDMA)) is a street drug which gained widespread use in the 'club' scene, likely due to the typical behavioral effects of MDMA which are described as an increase in empathy and friendliness. These prosocial effects led to MDMA being categorized as a separate drug class called 'entactogens'. In spite of abundant attention in the scientific literature, the mechanism of MDMAs prosocial effects has not been elucidated in humans, although animal research has suggested that the neuropeptide oxytocin may mediate these MDMA effects [1]. Oxytocin has recently received abundant attention for it's role in social behavior and has been suggested to induce prosocial and affiliative behavior in animals as well as in humans [2]. Objective: To investigate the effect of MDMA on oxytocin levels and subjective prosocial feelings in humans. Methods: In a double blind, randomized, crossover, and placebo-controlled study in fifteen healthy volunteers we investigated whether 100mg orally administered MDMA induces oxytocin release in humans. Blood samples for analysis of MDMA and oxytocin concentration were collected repeatedly during the study day. Subjective prosocial effects were assessed using two sub scales of the Bond and Lader (Visual Analogue) Mood Rating Scale (BLMRS) that specifically assess prosocial effects (antagonistic/amicable and withdrawn/gregarious). Statistical evaluation of drug effects (using SPSS 14 for Windows) was performed with a mixed model analysis of variance with drug and time as fixed factors and subject as random factor. Results: Mean MDMA maximal plasma concentrations (Cmax) were 222.7 μg/l (SD = 38.1 μg/l) 105 minutes after drug administration, and showed minimal decline (174.6 μg/l (SD = 40.0 μg/l) 300 minutes after drug administration). Oxytocin concentrations were significantly increased after MDMA administration [F(1,223)=84.5, p