Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Development of medications that attenuate symptoms of nicotine withdrawal may be useful for facilitating smoking cessation. The neuropeptide oxytocin (OXY) decreases withdrawal signs and other addiction-related effects of several drugs of abuse in animals, but has not been examined in a preclinical model of nicotine addiction. The goal of this study was to examine the effects of OXY on nicotine withdrawal in rats, measured as increases in somatic signs and elevations in intracranial self-stimulation (ICSS) thresholds (anhedonia-like behavior) during antagonist-precipitated withdrawal from a chronic nicotine infusion. Effects of OXY on baseline ICSS thresholds in non-dependent rats were also evaluated. OXY (0.06 - 1.0mg/kg, i.p.) blocked withdrawal-induced elevations in somatic signs in nicotine-dependent rats without affecting somatic signs in non-dependent rats. In contrast, OXY did not affect nicotine withdrawal-induced elevations in ICSS thresholds. Relatively high doses of OXY (0.75 or 2.0mg/kg) elevated baseline ICSS thresholds in non-dependent rats. These findings demonstrate that OXY blocks somatic signs but not elevations in ICSS thresholds during antagonist-precipitated nicotine withdrawal. The ability of higher OXY doses to elevate baseline ICSS thresholds in non-dependent rats may reflect an aversive and/or motoric effect. These data suggest that OXY-based medications may be useful for treating the somatic component of the nicotine withdrawal syndrome, but may not be effective in attenuating withdrawal-induced anhedonia.
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PMID:Effects of oxytocin on nicotine withdrawal in rats. 2423 89

Depression and anxiety can be severely detrimental to the health of both the affected woman and her offspring. In a rodent model of postpartum depression and anxiety, chronic social stress exposure during lactation induces deficits in maternal care and increases anxiety. Here, we extend previous findings by expanding the behavioral analyses, assessing lactation, and examining several neural systems within amygdalar and hypothalamic regions involved in the control of the stress response and expression of maternal care that may be mediating the behavioral changes in stressed dams. Compared with control dams, those exposed to chronic social stress beginning on day 2 of lactation show impaired maternal care and lactation and increased maternal anxiety on day 9 of lactation. Saccharin-based anhedonia and maternal aggression were increased and lactation was also impaired on day 16 of lactation. These behavioral changes were correlated with a decrease in oxytocin mRNA expression in the medial amygdala, and increases in the expressions of corticotrophin-releasing hormone mRNA in the central nucleus of the amygdala, glucocorticoid receptor mRNA in the paraventricular nucleus, and orexin 2 receptor mRNA in the supraoptic nucleus of stressed compared with control dams. The increase in glucocorticoid receptor mRNA in the paraventricular nucleus was negatively correlated with methylation of a CpG site in the promoter region. In conclusion, the data support the hypothesis that social stress during lactation can have profound effects on maternal care, lactation, and anxiety, and that these behavioral effects are mediated by central changes in stress and maternally relevant neuropeptide systems.
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PMID:Social stress during lactation, depressed maternal care, and neuropeptidergic gene expression. 2606 53

Schizophrenia is a chronic debilitating neuropsychiatric disorder estimated to affect 51 million people worldwide. Several symptom domains characterize schizophrenia, including negative symptoms, such as social withdrawal and anhedonia, cognitive impairments, such as disorganized thinking and impaired memory, and positive symptoms, such as hallucinations and delusions. While schizophrenia is a complex neuropsychiatric disorder with no single "cause," there is evidence that the oxytocin (Oxt) system may be dysregulated in some individuals. Further, treatment with intranasal Oxt reduces some of the heterogeneous symptoms associated with schizophrenia. Since Oxt is known for its modulatory effects on a variety of social and non-social behaviors, it is perhaps not surprising that it may contribute to some aspects of schizophrenia and could also be a useful therapeutic agent. In this review, we highlight what is known about Oxt's contributions to schizophrenia and schizophrenia-related behaviors and discuss its potential as a therapeutic agent.
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PMID:A Role for Oxytocin in the Etiology and Treatment of Schizophrenia. 2608 15

Tree shrews, a species phylogenetically close to primates, are regarded as a suitable and naturalistic animal model for depression studies. However, psychological symptoms that are essential for depression diagnosis and treatment, such as helplessness and social withdrawal, have not been studied in this model. Therefore, in this study, we first investigated learned helplessness, social interaction and sucrose preference induced by two chronic stress paradigms: uncontrollable foot shocks (1-week foot shocks) and multiple unpredictable stimuli (1-week foot shocks and 3-week unpredictable stressors) in tree shrews. Our results showed that uncontrollable foot shocks could only induce learned helplessness in animals; whereas animals treated with multiple unpredictable stimuli exhibited more depression-like behaviors including social withdrawal, anhedonia and learned helplessness. These findings suggested that multiple unpredictable stimuli could effectively induce various depression-like behaviors in tree shrews. More importantly, we compared the antidepressant effects of fluoxetine and carbetocin, a long-acting oxytocin analog, on specific depression-like behaviors. Our present data displayed that, compared with fluoxetine, carbetocin was also effective in reversing learned helplessness, elevating sucrose preference and improving social interaction behaviors in depression-like animals. Therefore, carbetocin might be a potential antidepressant with applications in humans.
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PMID:Depression-like behaviors in tree shrews and comparison of the effects of treatment with fluoxetine and carbetocin. 2698 70

Novel pharmacotherapies that improve outcomes for individuals with stress-related psychiatric disorders are needed. The neurohormone oxytocin (OT) is a promising candidate given its influence on the social-emotional brain. In this review, we present an overview of evidence supporting OT's utility for treating major depressive disorder and posttraumatic stress disorder. We first discuss endogenous OT, which research suggests is not yet a reliable biomarker of stress-related disorders. Second, we review effects of intranasal (IN) OT on processes relevant to stress-related disorders in healthy populations (anhedonia, reward processing, psychosocial stress reactivity, fear/anxiety, and social behavior) and their neurobiological mechanisms (e.g., the salience network and hypothalamic-pituitary-adrenal axis). Third, we present the sparse but promising findings from clinical populations, followed by discussion of critical moderating variables to consider in the service of maximizing the therapeutic potential of OT (e.g., patient sex and child maltreatment). We also identify heterogeneous findings and limitations of existing research, including reliance on single-dose studies in psychiatrically healthy samples and unanswered questions regarding the effectiveness of IN drug delivery and dosing schedules. Well-controlled multidose studies including women and measures of potentially moderating variables are sorely needed and would inform our understanding of the utility of OT for preventing and treating stress-related psychiatric disorders.
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PMID:Oxytocin and Stress-related Disorders: Neurobiological Mechanisms and Treatment Opportunities. 2864 72

Chronic stressors, such as chronic isolation in social mammals, can elevate glucocorticoids, which can affect cellular mechanisms of aging, including increased levels of oxidative stress and shortened telomere lengths. Recent work in the selectively social prairie vole (Microtus ochrogaster) suggests that oxytocin and social support may mitigate some of the negative consequences of social isolation, possibly by reducing glucocorticoid levels. We investigated the influences of isolation, social support, and daily oxytocin injections in female prairie voles. Glucocorticoid levels, oxidative damage, telomere length, and anhedonia, a behavioral index of depression, were measured throughout the study. We found that six weeks of chronic isolation led to increased glucocorticoid levels, oxidative damage, telomere degradation and anhedonia. However, daily oxytocin injections in isolated voles prevented these negative consequences. These findings demonstrate that chronic social isolation in female prairie voles is a potent stressor that results in depression-like behavior and accelerated cellular aging. Importantly, oxytocin can completely prevent the negative consequences of social isolation.
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PMID:Oxytocin administration prevents cellular aging caused by social isolation. 3064 38

The clinical picture of depressive disorders is characterized by a plethora of somatic symptoms, psychomotor retardation, and, particularly, anhedonia. The number of patients with residual symptoms or treatment resistance is high. Touch is the basic communication among humans and animals. Its application professionally in the form of, e.g., psychoactive massage therapy, has been shown in the past to reduce the somatic and mental symptoms of depression and anxiety. Here, we investigated the effects of a specially developed affect-regulating massage therapy (ARMT) vs. individual treatment with a standardized relaxation procedure, progressive muscle relaxation (PMR), in 57 outpatients with depression. Patients were given one ARMT or PMR session weekly over 4 weeks. Changes in somatic and cognitive symptoms were assessed by standard psychiatric instruments (Hamilton Depression Scale (HAMD) and the Bech-Rafaelsen-Melancholia-Scale (BRMS)) as well as a visual analogue scale. Furthermore, oral statements from all participants were obtained in semi-structured interviews. The findings show clear and statistically significant superiority of ARMT over PMR. The results might be interpreted within various models. The concept of interoception, as well as the principles of body psychotherapy and phenomenological aspects, offers cues for understanding the mechanisms involved. Within a neurobiological context, the significance of C-tactile afferents activated by special touch techniques and humoral changes such as increased oxytocin levels open additional ways of interpreting our findings.
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PMID:Effects of Psychoactive Massage in Outpatients with Depressive Disorders: A Randomized Controlled Mixed-Methods Study. 3299 75

Postpartum depression is a mood disorder with a distinct neurobiological and behavioural profile occurring during and after the postpartum period. Dopamine pathways in the limbic regions of the brain such as the nucleus accumbens (NAc) have been shown to be involved in the etiology of depressive disorders. Selective activation of the dopamine D1-D2 receptor heteromer has been demonsrated to cause depressive- and anxiogenic-like behaviours in rats. The maternal separation model involving three hour daily maternal separation (MS) from pups on PPD 2-15 on anxiety-, depression- and anhedonia-like behaviors in the dams was investigated, together with plasma corticosterone, oxytocin and D1-D2 heteromer expression in the NAc core and shell in non-MS and MS dams. Depression, anxiety and anhedonia-like behaviours were measured using the forced swim test, elevated plus maze and sucrose preference test, respectively. In comparison to non-MS controls, MS dams displayed slightly higher depressive and anxiety-like behaviours with no difference in anhedonia-like behaviours. The MS dams displayed significantly increased care of pups after their retrieval with higher bouts of nursing, lower latency to nurse, lower bouts of out nest behaviour and decreased self-care. There was no significant alteration in D1-D2 heteromer expression in NAc core and shell between mothers of either group (MS, non-MS) or between postpartum rats and nonpregnant female rats, remaining higher than in male rats. This data provides evidence for the maternal separation model in producing a postpartum depression-like profile, but with maternal resilience able to modify behaviours to counteract any potential deleterious consequences to the pups.
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PMID:Maternal Separation Model of Postpartum Depression: Potential Role for Nucleus Accumbens Dopamine D1-D2 Receptor Heteromer. 3305 44