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dynorphin a

Rachel I Anderson, David E Moorman, Howard C Becker
Understanding the neural systems that drive alcohol motivation and are disrupted in alcohol use disorders is of critical importance in developing novel treatments. The dynorphin and orexin/hypocretin neuropeptide systems are particularly relevant with respect to alcohol use and misuse. Both systems are strongly associated with alcohol-seeking behaviors, particularly in cases of high levels of alcohol use as seen in dependence. Furthermore, both systems also play a role in stress and anxiety, indicating that disruption of these systems may underlie long-term homeostatic dysregulation seen in alcohol use disorders...
March 11, 2018: Handbook of Experimental Pharmacology
Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Takeshi Iwasa, Kiyohito Yano, Yiliyasi Mayila, Takako Tokui, Rie Yanagihara, Sumika Matsui, Takeshi Kato, Akira Kuwahara, Minoru Irahara
Kisspeptin/neurokinin B (NKB)/dynorphin (Dyn) (KNDy) neuron in hypothalamic arcuate nucleus plays a key role in GnRH/LH pulsatile secretion. We aimed to determine whether stimulation of NKB/neurokinin 3 receptor (NK3R) signaling and inhibition of Dyn/kappa-opioid receptor (KOR) signaling recover LH secretion that is suppressed by acute fasting in male rats. Furthermore, we determined dose dependent effect of NKB/NK3R signaling on serum LH level under acute fasting condition in male mice. Mature male rats were injected saline (0...
February 23, 2018: Endocrine Journal
Duy-Khanh Dang, Eun-Joo Shin, Dae-Joong Kim, Hai-Quyen Tran, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Jung Hwan Jeong, Jae Kyung Byun, Sung Kwon Ko, Guoying Bing, Jau-Shyong Hong, Hyoung-Chun Kim
BACKGROUND: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice...
February 21, 2018: Journal of Neuroinflammation
Palmisano Martina, Caputi Francesca Felicia, Mercatelli Daniela, Romualdi Patrizia, Candeletti Sanzio
The dynorphinergic system is involved in pain transmission at spinal level, where dynorphin exerts antinociceptive or pronociceptive effects, based on its opioid or non-opioid actions. Surprisingly, little evidence is currently available concerning the supraspinal role of the dynorphinergic system in pain conditions. The present study aimed to investigate whether neuropathic pain is accompanied by prodynorphin (Pdyn) and κ-opioid receptor (Oprk1) gene expression alterations in selected mouse brain areas. To this end, mice were subjected to chronic constriction injury of the right sciatic nerve and neuropathic pain behavioral signs were ascertained after 14 days...
February 12, 2018: Genes, Brain, and Behavior
Aleisha M Moore, Kathryn A Lucas, Robert L Goodman, Lique M Coolen, Michael N Lehman
Kisspeptin/Neurokinin B/Dynorphin (KNDy) neurons of the arcuate nucleus (ARC) play a key role in the regulation of fertility. The ability to detect features of KNDy neurons that are essential for fertility may require three-dimensional (3D) imaging of the complete population. Recently developed protocols for optical tissue clearing permits 3D imaging of neuronal populations in un-sectioned brains. However, these techniques have largely been described in the mouse brain. We report 3D imaging of the KNDy cell population in the whole rat brain and sheep hypothalamus using immunolabelling and modification of a solvent-based clearing protocol, iDISCO...
February 2, 2018: Scientific Reports
Igor Bazov, Daniil Sarkisyan, Olga Kononenko, Hiroyuki Watanabe, Tatiana Yakovleva, Anita C Hansson, Wolfgang H Sommer, Rainer Spanagel, Georgy Bakalkin
Molecular changes induced by excessive alcohol consumption may underlie formation of dysphoric state during acute and protracted alcohol withdrawal which leads to craving and relapse. A main molecular addiction hypothesis is that the upregulation of the dynorphin (DYN)/κ-opioid receptor (KOR) system in the nucleus accumbens (NAc) of alcohol-dependent individuals causes the imbalance in activity of D1- and D2 dopamine receptor (DR) expressing neural circuits that results in dysphoria. We here analyzed post-mortem NAc samples of human alcoholics to assess changes in prodynorphin (PDYN) and KOR (OPRK1) gene expression and co-expression (transcriptionally coordinated) patterns...
January 30, 2018: Molecular Neurobiology
Kelsey M Nation, Milena De Felice, Pablo I Hernandez, David W Dodick, Volker Neugebauer, Edita Navratilova, Frank Porreca
The response of diffuse noxious inhibitory controls (DNIC) is often decreased, or lost, in stress-related functional pain syndromes. Because the dynorphin/kappa opioid receptor (KOR) pathway is activated by stress, we determined its role in DNIC using a model of stress-induced functional pain. Male, Sprague-Dawley rats were primed for 7 days with systemic morphine resulting in opioid-induced hyperalgesia. Fourteen days after priming, when hyperalgesia was resolved, rats were exposed to environmental stress and DNIC was evaluated by measuring hind paw response threshold to noxious pressure (test stimulus) after capsaicin injection in the forepaw (conditioning stimulus)...
January 23, 2018: Pain
Dengyun Ge, Nickolas Anastasios Lavidis
Amphibian neuromuscular junctions become relatively more silent during the dry-winter season in Australia. Endogenous opioid peptides play an important role in the regulation of the physiological functions of active and dormant vertebrates. Previous findings suggest that dynorphin-A is more potent than other opiates in decreasing evoked neurotransmission in amphibian neuromuscular junctions. Dynorphin-A has been shown not to alter the amplitude or the frequency of spontaneous quantal neurotransmitter release...
January 17, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Loris L Ferrari, Daniel Park, Lin Zhu, Matthew R Palmer, Rebecca Y Broadhurst, Elda Arrigoni
Orexin (also known as hypocretin) neurons are considered a key component of the ascending arousal system. They are active during wakefulness, at which time they drive and maintain arousal, and are silent during sleep. Their activity is controlled by long-range inputs from many sources, as well as by more short-range inputs, including from presumptive GABAergic neurons in the lateral hypothalamus/perifornical region (LH/PF). To characterize local GABAergic input to orexin neurons we employed channelrhodopsin-2 (ChR2)-assisted-circuit-mapping in brain slices...
January 8, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Wei-Jie Fang, Thomas F Murray, Jane V Aldrich
Kappa (κ) opioid receptor selective antagonists are useful pharmacological tools in studying κ opioid receptors and have potential to be used as therapeutic agents for the treatment of a variety of diseases including mood disorders and drug addiction. Arodyn (Ac[Phe1-3,Arg4,d-Ala8]Dyn A-(1-11)NH2) is a linear acetylated dynorphin A (Dyn A) analog that is a potent and selective κ opioid receptor antagonist (Bennett et al. J Med Chem 2002;45:5617-5619) and prevents stress-induced reinstatement of cocaine-seeking behavior following central administration (Carey et al...
November 21, 2017: Bioorganic & Medicinal Chemistry
B Alvarez, T Barrientos, L Gac, J A Teske, C E Perez-Leighton
The dynorphin (DYN) peptide family includes opioid and non-opioid peptides, yet the physiological role of the non-opioid DYN peptides remains poorly understood. Recent evidence shows that administering the non-opioid peptide DYN-A2-17 into the paraventricular hypothalamic nucleus (PVN) simultaneously increased short-term intake of standard rodent chow and spontaneous physical activity (SPA). The present studies aimed to expand upon the mechanisms and role of DYN-A2-17 on food intake and energy expenditure. Injection of DYN-A2-17 in PVN increased SPA, energy expenditure and wheel running in the absence of food...
February 10, 2018: Neuroscience
Kimihiko Nakao, Kinuyo Iwata, Toshiyuki Takeshita, Hitoshi Ozawa
Zucker fatty (ZF) rats are considered to be an obese model due to leptin receptor abnormality and such rats show infertility. Pulsatile gonadotropin-releasing hormone/luteinizing hormone (LH) secretion, which is important for follicular development in females, is considered to be controlled by KNDy neurons coexpressing kisspeptin, neurokinin B (NKB), and dynorphin A (DynA), encoded by Kiss1, Tac3, and Pdyn, respectively, in the hypothalamic arcuate nucleus (ARC). The purpose of this study is to examine the expression of KNDy neurons in female ZF rats by histochemical approach because pulsatile LH secretion is suppressed...
February 5, 2018: Neuroscience Letters
Bruno Lunenfeld, Klaus Bühler
Since more than 100 years, it is known that pituitary function depends upon the function of higher centers in the brain. It was already assumed at this time that pituitary extracts could influence the gonads and postulated that their use could have practical applications. In 1926, the 'gonadal principle' was discovered revealing the regulation of ovarian function by the pituitary. The two pituitary hormones were called 'Prolan A' and 'Prolan B' which are responsible for ovarian function especially secretion of the hormones: 'lutein' and 'foliculin'...
November 24, 2017: Gynecological Endocrinology
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration...
November 13, 2017: Neurotoxicity Research
Hiroaki Okamura, Takashi Yamamura, Yoshihiro Wakabayashi
A population of neurons in the arcuate nucleus (ARC) coexpresses kisspeptin, neurokinin B (NKB), and dynorphin, and therefore they are referred to as KNDy neurons. It has been suggested that KNDy neurons participate in several brain functions, including the control of reproduction. The present study aimed to advance our understanding of the anatomy of the KNDy neural system. We first produced an antiserum against goat kisspeptin. After confirming its specificity, the antiserum was used to histochemically detect kisspeptin-positive signals...
November 7, 2017: Journal of Reproduction and Development
Moeko Kanaya, Kinuyo Iwata, Hitoshi Ozawa
Kisspeptin (KISS1; encoded by Kiss1 ) neurons in the arcuate nucleus (ARC) co-express tachykinin 3 (TAC3; also known as neurokinin B) and dynorphin A (PDYN). Accordingly, they are termed KNDy neurons and considered to be crucial in generating pulsatile release of gonadotropin-releasing hormone. Accumulating evidence suggests that Kiss1 and Tac3 are negatively regulated by estrogen. However it has not been fully determined whether and how estrogen modulates Pdyn and PDYN. Here, we examined the expression of Pdyn mRNA and PDYN by in situ hybridization and immunohistochemistry, respectively, in the ARC of female rats after ovariectomy (OVX) and OVX plus low or high-dose beta-estradiol (E 2 ) replacement...
October 24, 2017: Biology of Reproduction
Alessandra Matzeu, Marsida Kallupi, Olivier George, Paul Schweitzer, Rémi Martin-Fardon
The orexin (Orx) system plays a critical role in drug addiction and reward-related behaviors. The dynorphin (Dyn) system promotes depressive-like behavior and plays a key role in the aversive effects of stress. Orx and Dyn are co-released and have opposing functions in reward and motivation in the ventral tegmental area (VTA). Previous studies suggested that OrxA transmission in the posterior paraventricular nucleus of the thalamus (pPVT) participates in cocaine-seeking behavior. This study determined whether Orx and Dyn interact in the pPVT...
October 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Nai-Jiang Liu, Vijaya Murugaiyan, Emiliya M Storman, Stephen A Schnell, Arjun Kumar, Martin W Wessendorf, Alan R Gintzler
We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous μ-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle: minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and κ-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated metabotropic glutamate receptor 1 (mGluR1 ) signaling, are critical to the transition from an EM2 nonresponsive state (during diestrus) to an analgesically responsive state (during proestrus)...
November 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Igor Bazov, Daniil Sarkisyan, Olga Kononenko, Hiroyuki Watanabe, Mumtaz Malik Taqi, Lada Stålhandske, Dineke S Verbeek, Jan Mulder, Grazyna Rajkowska, Donna Sheedy, Jillian Kril, Xueguang Sun, Ann-Christine Syvänen, Tatiana Yakovleva, Georgy Bakalkin
Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF)...
July 28, 2017: Cerebral Cortex
Jade Cabestre Venancio, Lisandra Oliveira Margatho, Rodrigo Rorato, Roberta Ribeiro Costa Rosales, Lucas Kniess Debarba, Ricardo Coletti, Jose Antunes-Rodrigues, Carol F Elias, Lucila Leico K Elias
Leptin is a permissive factor for puberty initiation, participating as a metabolic cue in the activation of the kisspeptin (Kiss1)-gonadotropin-releasing hormone neuronal circuitry; however, it has no direct effect on Kiss1 neurons. Leptin acts on hypothalamic cocaine- and amphetamine-regulated transcript (CART) neurons, participating in the regulation of energy homeostasis. We investigated the influence of a short-term high-fat diet (HFD) on the effect of leptin on puberty timing. Kiss1-hrGFP female mice received a HFD or regular diet (RD) after weaning at postnatal day (PN)21 and were studied at PN28 and PN32...
November 1, 2017: Endocrinology
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