Opioid Modulation of Oxytocin Release

Morris, Mark S.; Domino, Edward F.

doi:10.1177/0091270010361256

Cited by 23 publications

(16 citation statements)

References 48 publications

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“…Moreover, although Lithium (You et al, 2001) and Valproate (Štefánik et al, 2015) are reported to increase OXT release in rats and to increase OXT mRNA expression in rat hypothalamic PVN and SON, the IOD of OXTimmunoreactivity of the mood disorder patients who had been administered these compounds (IOD: 24.41,27.39,and 18.06) were fully within the range of the other mood disorder patients (from 16.06 to 40.91, mean value 24.02). Furthermore, a benzodiazepine, such as chlordiazepoxide, was shown to inhibit OXT release in response to noxious stimuli (Yagi and Onaka, 1996), and chronic morphine treatment in rat inhibited OXT synthesis (Morris et al, 2010;You et al, 2001). In our study, more mood disorder patients (n = 9) than control subjects (n = 3) were given diazepines, and more mood disorder patients (n = 9) than control subjects (n = 3) were exposed to morphine.…”

Section: Discussionmentioning

confidence: 53%

Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders

Dai

Zhu

et al. 2017

Neuropsychopharmacol

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Oxytocin (OXT), synthesized in the hypothalamic paraventricular nucleus (PVN) and then released into different brain areas, may play a crucial role in various behaviors and neuropsychiatric disorders, including depression. Testosterone has been proposed by clinical studies to have the opposite effect of oxytocin in these disorders. We began by studying, in the postmortem hypothalamus of fifteen patients with mood disorders and fifteen matched controls, the expression of OXT in the PVN by means of immunocytochemistry (ICC) and the co-localization of OXT and androgen receptor (AR) by means of double labeling ICC. Subsequently, the regulatory effect of AR on OXT gene expression was studied in vitro. We found a higher expression of PVN OXT in the mood disorder patients than in the control subjects, and observed a clear co-localization of AR in OXT-expressing neurons, both in the cytoplasm and in the nucleus. In addition, a significant decrease in OXT-mRNA levels was observed after pre-incubation of the SK-N-SH cells with testosterone. A further potential androgen-responsive element in the human OXT gene promotor was revealed by electrophoretic mobility shift assays and co-transfections in neuroblastoma cells. Finally, in vitro studies demonstrated that AR mediated the down-regulation of OXT gene expression. These results suggest that the fact that OXT and testosterone appear to have opposite effects in neuropsychiatric disorders might be based upon a direct inhibition of AR on OXT transcription, which may provide a novel target for therapeutic strategies in depression.

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Section: Discussionmentioning

confidence: 53%

Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders

Dai

Zhu

et al. 2017

Neuropsychopharmacol

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“…One of the most common intrapartum procedures associated with synOT is epidural anesthesia. Since opioids have an inhibitory effect on secretion of oxytocin (via mu and kappa receptors) [79] synOT is often required after the administration of an epidural. While the half life of synOT is only 10–12 min or less [80] and intrapartum endogenous oxytocin levels correlate with synOT dosage rate [81], recent evidence suggests the interactions between epidural and synOT may modulate the oxytocin system beyond labor [82].…”

Section: Evaluation Of the Hypothesismentioning

confidence: 99%

The EPIIC hypothesis: Intrapartum effects on the neonatal epigenome and consequent health outcomes

et al. 2013

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There are many published studies about the epigenetic effects of the prenatal and infant periods on health outcomes. However, there is very little knowledge regarding the effects of the intrapartum period (labor and birth) on health and epigenetic remodeling. Although the intrapartum period is relatively short compared to the complete perinatal period, there is emerging evidence that this time frame may be a critical formative phase for the human genome. Given the debates from the National Institutes of Health and World Health Organization regarding routine childbirth procedures, it is essential to establish the state of the science concerning normal intrapartum epigenetic physiology. EPIIC (Epigenetic Impact of Childbirth) is an international, interdisciplinary research collaboration with expertise in the fields of genetics, physiology, developmental biology, epidemiology, medicine, midwifery, and nursing. We hypothesize that events during the intrapartum period – specifically the use of synthetic oxytocin, antibiotics, and cesarean section – affect the epigenetic remodeling processes and subsequent health of the mother and offspring. The rationale for this hypothesis is based on recent evidence and current best practice.

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“…Evidence of opioid–OXT interactions is indeed well established. Endogenous opioids are involved in the modulation of OXT release into the brain and the periphery via mu- and kappa-receptors expressed on OXT-secreting neurons (23–26). Even though the opioidergic modulation of OXT release may account for many shared effects, the interplay of these two systems does not probably end with that.…”

Section: Introductionmentioning

confidence: 99%

Region Specific Up-Regulation of Oxytocin Receptors in the Opioid Oprm1âˆ’/âˆ’ Mouse Model of Autism

et al. 2014

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Autism spectrum disorders (ASDs) are characterized by impaired communication, social impairments, and restricted and repetitive behaviors and interests. Recently, altered motivation and reward processes have been suggested to participate in the physiopathology of ASDs, and μ-opioid receptors (MORs) have been investigated in relation to social reward due to their involvement in the neural circuitry of reward. Mice lacking a functional MOR gene (Oprm1−/− mice) display abnormal social behavior and major autistic-like core symptoms, making them an animal model of autism. The oxytocin (OXT) system is a key regulator of social behavior and co-operates with the opioidergic system in the modulation of social behavior. To better understand the opioid-OXT interplay in the central nervous system, we first determined the expression of the oxytocin receptor (OXTR) in the brain of WT C57BL6/J mice by quantitative autoradiography; we then evaluated OXTR regional alterations in Oprm1−/− mice. Moreover, we tested these mice in a paradigm of social behavior, the male–female social interaction test, and analyzed the effects of acute intranasal OXT treatment on their performance. In autoradiography, Oprm1−/− mice selectively displayed increased OXTR expression in the Medial Anterior Olfactory Nucleus, the Central and Medial Amygdaloid nuclei, and the Nucleus Accumbens. Our behavioral results confirmed that Oprm1−/− male mice displayed social impairments, as indicated by reduced ultrasonic calls, and that these were rescued by a single intranasal administration of OXT. Taken together, our results provide evidence of an interaction between OXT and opioids in socially relevant brain areas and in the modulation of social behavior. Moreover, they suggest that the oxytocinergic system may act as a compensative mechanism to bypass and/or restore alterations in circuits linked to impaired social behavior.

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Opioid Modulation of Oxytocin Release

Cited by 23 publications

References 48 publications

Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders

Direct Involvement of Androgen Receptor in Oxytocin Gene Expression: Possible Relevance for Mood Disorders

The EPIIC hypothesis: Intrapartum effects on the neonatal epigenome and consequent health outcomes

Region Specific Up-Regulation of Oxytocin Receptors in the Opioid Oprm1âˆ’/âˆ’ Mouse Model of Autism

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