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Corticosteroids and nucleus accumbens

Steven F Merkel, Allison M Andrews, Evan M Lutton, Roshanak Razmpour, Lee Anne Cannella, Servio H Ramirez
Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent preclinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay...
July 2017: Cell Transplantation
Steven Merkel, Allison Andrews, Evan Lutton, Roshanak Razmpour, Lee Cannella, Servio Ramirez
Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent pre-clinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here, we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay...
November 29, 2016: Cell Transplantation
Bárbara S Pinheiro, Cristina Lemos, Fernanda Neutzling Kaufmann, Joana M Marques, Carla S da Silva-Santos, Eugénia Carvalho, Ken Mackie, Ricardo J Rodrigues, Rodrigo A Cunha, Attila Köfalvi
Here we asked if insulin activation of the nucleus accumbens in vitro is reflected by an increase in (3)H-deoxyglucose ([(3)H]DG) uptake, thus subserving a new model to study molecular mechanisms of central insulin actions. Additionally, we investigated the dependence of this insulin effect on endocannabinoids and corticosteroids, two major culprits in insulin resistance. We found that in acute accumbal slices, insulin (3 and 300nM but not at 0.3nM) produced an increase in [(3)H]DG uptake. The synthetic cannabinoid agonist, WIN55212-2 (500nM) and the glucocorticoid dexamethasone (10μM), impaired insulin (300nM) action on [(3)H]DG uptake...
June 2016: Brain Research Bulletin
Jennifer N Berry, Meredith A Saunders, Lynda J Sharrett-Field, Anna R Reynolds, Michael T Bardo, James R Pauly, Mark A Prendergast
Elevations in circulating corticosteroids during periods of stress may influence activity of the mesolimbic dopamine reward pathway by increasing glutamatergic N-methyl-D-aspartate (NMDA) receptor expression and/or function in a glucocorticoid receptor-dependent manner. The current study employed organotypic co-cultures of the ventral tegmental area (VTA) and nucleus accumbens (NAcc) to examine the effects of corticosterone exposure on NMDA receptor-mediated neuronal viability. Co-cultures were pre-exposed to vehicle or corticosterone (CORT; 1 μM) for 5 days prior to a 24 h co-exposure to NMDA (200 μM)...
January 2016: Brain Research Bulletin
Darcy Litteljohn, Eric Nelson, Shawn Hayley
Cytokines are inflammatory messengers that orchestrate the brain's response to immunological challenges, as well as possibly even toxic and psychological insults. We previously reported that genetic ablation of the pro-inflammatory cytokine, interferon-gamma (IFN-γ), attenuated some of the corticosteroid, cytokine, and limbic dopaminergic variations induced by 6 weeks of exposure to an unpredictable psychologically relevant stressor. Presently, we sought to determine whether a lack of IFN-γ would likewise modify the impact of chronic stress on hippocampus-dependent memory function and related neurotransmitter and neurotrophin signaling systems...
2014: Frontiers in Cellular Neuroscience
Paul J Lucassen, Jens Pruessner, Nuno Sousa, Osborne F X Almeida, Anne Marie Van Dam, Grazyna Rajkowska, Dick F Swaab, Boldizsár Czéh
Environmental challenges are part of daily life for any individual. In fact, stress appears to be increasingly present in our modern, and demanding, industrialized society. Virtually every aspect of our body and brain can be influenced by stress and although its effects are partly mediated by powerful corticosteroid hormones that target the nervous system, relatively little is known about when, and how, the effects of stress shift from being beneficial and protective to becoming deleterious. Decades of stress research have provided valuable insights into whether stress can directly induce dysfunction and/or pathological alterations, which elements of stress exposure are responsible, and which structural substrates are involved...
January 2014: Acta Neuropathologica
Maria Stratinaki, Artemis Varidaki, Vasiliki Mitsi, Subroto Ghose, Jane Magida, Caroline Dias, Scott J Russo, Vincent Vialou, Barbara J Caldarone, Carol A Tamminga, Eric J Nestler, Venetia Zachariou
Regulator of G protein signaling 4 (Rgs4) is a signal transduction protein that controls the function of monoamine, opiate, muscarinic, and other G protein-coupled receptors via interactions with Gα subunits. Rgs4 is expressed in several brain regions involved in mood, movement, cognition, and addiction and is regulated by psychotropic drugs, stress, and corticosteroids. In this study, we use genetic mouse models and viral-mediated gene transfer to examine the role of Rgs4 in the actions of antidepressant medications...
May 14, 2013: Proceedings of the National Academy of Sciences of the United States of America
Elena Sivukhina, Hans H Schäfer, Gustav F Jirikowski
Endocrine regulation of central and systemic stress response as well as learning and memory are in part controlled by systemic glucocorticoid levels. So far steroids have been thought to act on the brain predominantly through nuclear receptors. However, some brain systems known to respond to glucocorticoids seem to be devoid of the respective receptor proteins (GR). It is likely that known central actions of adrenal steroids may also be mediated by non-genomic actions involving intrinsic binding globulins. In recent studies we described the intrinsic expression of corticosteroid-binding globulin (CBG) in rat, mouse and human brains...
May 2013: Annals of Anatomy
Leandro F Vendruscolo, Estelle Barbier, Joel E Schlosburg, Kaushik K Misra, Timothy W Whitfield, Marian L Logrip, Catherine Rivier, Vez Repunte-Canonigo, Eric P Zorrilla, Pietro P Sanna, Markus Heilig, George F Koob
Alcoholism is characterized by a compulsion to seek and ingest alcohol, loss of control over intake, and the emergence of a negative emotional state during abstinence. We hypothesized that sustained activation of neuroendocrine stress systems (e.g., corticosteroid release via the hypothalamic-pituitary-adrenal axis) by alcohol intoxication and withdrawal and consequent alterations in glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) activation drive compulsive alcohol drinking. Our results showed that rats exposed to alcohol vapor to the point of dependence displayed increased alcohol intake, compulsive drinking measured by progressive-ratio responding, and persistent alcohol consumption despite punishment, assessed by adding quinine to the alcohol solution, compared with control rats that were not exposed to alcohol vapor...
May 30, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mário Oliveira, Pedro Leão, Ana-João Rodrigues, José-Miguel Pêgo, João-José Cerqueira, Nuno Sousa
INTRODUCTION: Brain regions implicated in sexual behavior begin to differentiate in the last trimester of gestation. Antenatal therapy with corticosteroids is often used in clinical practice during this period to accelerate lung maturation in preterm-risk pregnancies. Clinical and animal studies highlighted major behavioral impairments induced later in life by these treatments, especially when synthetic corticosteroids are used. AIM: To evaluate the implications of acute prenatal treatment with natural vs...
July 2011: Journal of Sexual Medicine
Melanie D Klok, Simone R Alt, Alicia J M Irurzun Lafitte, Jonathan D Turner, Egbert A J F Lakke, Inge Huitinga, Claude P Muller, Frans G Zitman, E Ronald de Kloet, Roel H Derijk
Appropriate signaling in the brain by the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) is critical in regulation of the hypothalamic-pituitary-adrenal (HPA) axis, emotional arousal and cognitive performance. To date, few data exist on MR (and GR) expression in the brain of patients suffering from major depressive disorder (MDD). With the help of quantitative PCR we assessed MR and GR mRNA expression, including the splice variants MRα and MRβ, in tissue samples from the hippocampus, amygdala, inferior frontal gyrus, cingulate gyrus and nucleus accumbens...
July 2011: Journal of Psychiatric Research
Susannah J Tye, Anthony D Miller, Charles D Blaha
Corticosteroid receptor modulation of mesoaccumbens dopamine neurotransmission is believed to be a key neurobiological mechanism mediating the effects of stress in addiction. Importantly, nucleus accumbens (NAc) subregions (core and shell) are reported to respond differentially to fluctuating basal levels of glucocorticoids, with dopaminergic responses in the core of the NAc being somewhat impervious to fluctuating levels of glucocorticoids relative to the shell. To investigate the corticosteroid receptor mechanisms mediating basal dopamine efflux in the core of the NAc, we have used chronoamperometry in combination with stearate-modified graphite paste electrodes in urethane anesthetized male Long-Evans rats during the peak and nadir of the circadian cycle...
November 2009: Synapse
Julio César Morales-Medina, Fremioht Sanchez, Gonzalo Flores, Yvan Dumont, Rémi Quirion
Elevated levels of corticosteroids and stress play key roles in the pathophysiology of affective disorders. Corticosterone (CORT)-treated rats have emerged as a pharmacological model of depression-like behaviors. Previous studies have shown that CORT administration induces neuronal atrophy in the CA3 subfield of the hippocampus and laminae II/III of the prefrontal cortex. However, little attention has been given to other limbic structures such as the amygdala and the nucleus accumbens (NAcc). We investigated here whether 3 weeks of CORT administration in rats causes dendritic remodeling and spine density reorganization in the basolateral amygdala and pyramidal neurons of the CA1 subfield of the hippocampus as well as in spiny medium neurons of NAcc...
December 2009: Journal of Chemical Neuroanatomy
Matthew R Campioni, Ming Xu, Daniel S McGehee
Stress hormones released in the CNS following exposure to unavoidable, aversive stimuli have been shown to alter the physiology of neurons in multiple brain regions including hippocampus, amygdala, prefrontal cortex, and ventral tegmental area. The nucleus accumbens (NAc), a motor-limbic interface linked to motivation and reward, receives inputs from each of these stress-affected brain regions, raising the possibility that its function might also be altered in response to stress. To assess potential stress-induced plasticity in the NAc, we exposed adult mice to daily cold water forced swim for 2 consecutive days and conducted electrophysiological experiments assessing glutamate receptor function in brain slices taken 18-24 h following the second swim...
June 2009: Journal of Neurophysiology
G A Coria-Avila, M E Hernández-Aguilar, R Toledo-Cárdenas, L I García-Hernández, J Manzo, P Pacheco, M Miquel, J G Pfaus
AIM: To analyse the biological and neural bases of partner preference formation in rodents as models to understand human pair bonding. DEVELOPMENT: Rodents are social individuals, capable of forming short- or long-lasting partner preferences that develop slowly by stimuli like cohabitation, or rapidly by stimuli like sex and stress. Dopamine, corticosteroids, oxytocin, vasopressin, and opioids form the neurochemical substrate for pair bonding in areas like the nucleus accumbens, the prefrontal cortex, the piriform cortex, the medial preoptic area, the ventral tegmental area and the medial amygdala, among others...
August 16, 2008: Revista de Neurologia
Meng Yao, Fang Hu, Robert J Denver
Glucocorticoids (GCs) play essential roles in physiology, development, and behavior that are mediated largely by the glucocorticoid receptor (GR). Although the GR has been intensively studied in mammals, very little is known about the GR in nonmammalian tetrapods. We analyzed the distribution and GC regulation of GR in the brain of the frog Xenopus laevis by immunohistochemistry. GR-immunoreactive (GR-ir) cells were widely distributed, with the highest densities in the medial pallium (mp; homolog of the mammalian hippocampus), accumbens, anterior preoptic area (POA; homolog of the mammalian paraventricular nucleus), Purkinje cell layer of the cerebellum, and rostral anterior pituitary gland (location of corticotropes)...
June 20, 2008: Journal of Comparative Neurology
Richard G Hunter, Aleksandra Vicentic, George Rogge, Michael J Kuhar
CART (Cocaine- and Amphetamine-Regulated Transcript) was initially described as an mRNA which had increased expression in the rat striatum following administration of acute cocaine or amphetamine but not saline. However, not all subsequent studies confirmed this. The present study aimed to repeat experiments with conflicting results and to reexamine and extend the original finding of acute regulation of nucleus accumbens CART mRNA by cocaine. Acute administration of cocaine failed to produce any change in levels of CART mRNA or peptide...
July 4, 2005: European Journal of Pharmacology
Michela Marinelli, Pier Vincenzo Piazza
In this review we summarize data obtained from animal studies showing that glucocorticoid hormones have a facilitatory role on behavioural responses to psychostimulant drugs such as locomotor activity, self-administration and relapse. These behavioural effects of glucocorticoids involve an action on the meso-accumbens dopamine system, one of the major systems mediating the addictive properties of drugs of abuse. The effects of glucocorticoids in the nucleus accumbens are site-specific; these hormones modify dopamine transmission in only the shell of this nucleus without modifying it in the core...
August 2002: European Journal of Neuroscience
M.A. Gingras, A.R. Cools
The aim of the study was to determine whether high responders (HR) and low responders (LR) to novelty, selected from an outbred Wistar rat population, show differences in ethanol consumption. HR and LR differ in catecholaminergic activity in the nucleus accumbens as well as in brain sensitivity to corticosteroids, biological features believed to play a role in ethanol consumption. Due to these differences it was predicted that HR would consume less ethanol and show less preference than would LR. Animals were maintained on a schedule of alternative day presentation of ethanol...
November 1995: Behavioural Pharmacology
M Marinelli, B Aouizerate, M Barrot, M Le Moal, P V Piazza
Previous work has shown that glucocorticoid hormones facilitate the behavioral and dopaminergic effects of morphine. In this study we examined the possible role in these effects of the two central corticosteroid receptor types: mineralocorticoid receptor (MR), and glucocorticoid receptor (GR). To accomplish this, specific antagonists of these receptors were infused intracerebroventricularly and 2 hr later we measured: (i) locomotor activity induced by a systemic injection of morphine (2 mg/kg); (ii) locomotor activity induced by an infusion of morphine (1 microg per side) into the ventral tegmental area, which is a dopamine-dependent behavioral response to morphine; (iii) morphine-induced dopamine release in the nucleus accumbens, a dopaminergic projection site mediating the locomotor and reinforcing effects of drugs of abuse...
June 23, 1998: Proceedings of the National Academy of Sciences of the United States of America
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