scholarly journals Effect of Glucocorticoid Receptor Antagonism on Alcohol Self-Administration in Genetically-Selected Marchigian Sardinian Alcohol-Preferring and Non-Preferring Wistar Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 4184
Author(s):  
Federica Benvenuti ◽  
Nazzareno Cannella ◽  
Serena Stopponi ◽  
Laura Soverchia ◽  
Massimo Ubaldi ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Blood Levels ◽  
Self Administration ◽  
Saccharin Intake ◽  
Systemic Injection ◽  
Male And Female ◽  
Selective Blockade ◽  
Negative Emotional State ◽  
Nonspecific Effects ◽  
Before And After

Alcoholism is a chronically relapsing disorder characterized by high alcohol intake and a negative emotional state during abstinence, which contributes to excessive drinking and susceptibility to relapse. Stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and alterations in glucocorticoid receptor (GR) function have been linked to transition from recreational consumption to alcohol use disorder (AUD). Here, we investigated the effect of pharmacological antagonisms of GR on alcohol self-administration (SA) using male and female Wistar and Marchigian Sardinian alcohol-preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and highly sensitive to stress. Animals were trained to self-administer 10% (v/v) alcohol. Once a stable alcohol SA baseline was reached, we tested the effect of the GR antagonists mifepristone (0.0, 10, 30 and 60 mg/kg; i.p.) and CORT113176 (0.0, 10, 30 and 60 mg/kg) on alcohol SA. To evaluate whether the effects of the two compounds were specific for alcohol, the two drugs were tested on a similar saccharin SA regimen. Finally, basal blood corticosterone (CORT) levels before and after alcohol SA were determined. Systemic injection with mifepristone dose-dependently reduced alcohol SA in male and female Wistars but not in msPs. Administration of CORT113176 decreased alcohol SA in male and female Wistars as well as in female msPs but not in male msP rats. At the highest dose, mifepristone also reduced saccharin SA in male Wistars and female msPs, suggesting the occurrence of some nonspecific effects at 60 mg/kg of the drug. Similarly, the highest dose of CORT113176 (60 mg/kg) decreased saccharin intake in male Wistars. Analysis of CORT levels revealed that females of both rat lines had higher blood levels of CORT compared to males. Alcohol consumption reduced CORT in females but not in males. Overall, these findings indicate that selective blockade of GR selectively reduces alcohol SA, and genetically selected msP rats are less sensitive to this pharmacological manipulation compared to heterogeneous Wistars. Moreover, results suggest sex differences in response to GR antagonism and the ability of alcohol to regulate GR transmission.

scholarly journals Does the Therapist’s Sex Affect the Psychological Effects of Sports Massage?—A Quasi-Experimental Study

2020 ◽  
Vol 10 (6) ◽  
pp. 376 ◽  
Author(s):  
Bernhard Reichert
Keyword(s):  
High Performance ◽  
Emotional State ◽  
Sexual Attraction ◽  
Wait Time ◽  
Similar Group ◽  
Male And Female ◽  
Personnel Planning ◽  
Nonspecific Effects ◽  
Before And After ◽  
Quasi Experimental

Objectives: The aim of this study was to determine the influence of the sex of the therapist and of the athlete on the athlete’s current emotional state after a sports massage. The assumption was that the effect of a massage on the current mood was independent of the sex of the therapists or athletes. Background: Sports massages are an integral part of the support given to athletes during training or competition and are a commonly used method for promoting athletes’ physical and mental recovery. Few studies have measured the mental characteristics or even the nonspecific effects of sports massages. Sexual attraction or dislike are among the nonspecific effects of a treatment. Materials and methods: One hundred and sixty-eight high-performance male and female amateur athletes received a sports massage from 15 male and female trained therapists. The current emotional state of the athletes was measured before and after intervention using the BSKE-EA17 adjective scale, whose items can be assigned to five categories of the current emotional state. ANOVAs (analysis of covariances) were carried out to calculate the interactions between the sexes. Cohen’s d for similar group sizes and similar group variances were determined. Results: Neither the sex of the therapist nor the sex of the athlete had any influence on the mental effect of a sports massage. The only exception was when male athletes were treated by female therapists, where an increase in “elevated mood” was observed. Sports massages resulted in an increase in the responses in the categories “elevated mood” (d = 1.1) and “level of activation” (d = 0.3) and a decrease in the responses for “low mood” (d = 0.3), “level of deactivation” (d = 0.6) and “level of excitation” after the massage compared to before the massage (d = 0.9). Conclusions: Sports massages appear to increase the positive dimensions of the athletes’ current emotional state and reduce the negative dimensions. The self-reported mood changes from before the massage to after the massage were not influenced by other prognostic variables, including wait time, age of the athlete or the duration of the run. The results suggest that the specific effects of sports massages on the mental status are supported. Disregarding the aspect of the therapists’ sex, sports officials, trainers and athletes therefore can be more independent in the personnel planning of sports therapists.

The Clinical, Roentgenological and Morphological Effects of an Acute Exposure of Phosgene on the Lungs of Dogs

1971 ◽  
Vol 29 ◽  
pp. 236-237
Author(s):  
R. F. Bils ◽  
W. F. Diller ◽  
F. Huth
Keyword(s):  
Latent Period ◽  
Chemical Industry ◽  
Toxic Substance ◽  
Lung Edema ◽  
X Rays ◽  
Beagle Dogs ◽  
Male And Female ◽  
Morphological Alterations ◽  
Before And After ◽  
Electron Microscopes

Phosgene still plays an important role as a toxic substance in the chemical industry. Thiess (1968) recently reported observations on numerous cases of phosgene poisoning. A serious difficulty in the clinical handling of phosgene poisoning cases is a relatively long latent period, up to 12 hours, with no obvious signs of severity. At about 12 hours heavy lung edema appears suddenly, however changes can be seen in routine X-rays taken after only a few hours' exposure (Diller et al., 1969). This study was undertaken to correlate these early changes seen by the roengenologist with morphological alterations in the lungs seen in the'light and electron microscopes.Forty-two adult male and female Beagle dogs were selected for these exposure experiments. Treated animals were exposed to 94.5-107-5 ppm phosgene for 10 min. in a 15 m3 chamber. Roentgenograms were made of the thorax of each animal before and after exposure, up to 24 hrs.

scholarly journals Spinal Muscular Atrophy after Nusinersen Therapy: Improved Physiology in Pediatric Patients with No Significant Change in Urine, Serum, and Liquor 1H-NMR Metabolomes in Comparison to an Age-Matched, Healthy Cohort

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 206
Author(s):  
Leon Deutsch ◽  
Damjan Osredkar ◽  
Janez Plavec ◽  
Blaž Stres
Keyword(s):  
Machine Learning ◽  
Spinal Muscular Atrophy ◽  
1H Nmr ◽  
Pediatric Patients ◽  
Muscular Atrophy ◽  
Male And Female ◽  
Before And After ◽  
Healthy Cohort ◽  
Males And Females ◽  
Urine Serum

Spinal muscular atrophy (SMA) is a genetically heterogeneous group of rare neuromuscular diseases and was until recently the most common genetic cause of death in children. The effects of 2-month nusinersen therapy on urine, serum, and liquor 1H-NMR metabolomes in SMA males and females were not explored yet, especially not in comparison to the urine 1H-NMR metabolomes of matching male and female cohorts. In this prospective, single-centered study, urine, serum, and liquor samples were collected from 25 male and female pediatric patients with SMA before and after 2 months of nusinersen therapy and urine samples from a matching healthy cohort (n = 125). Nusinersen intrathecal application was the first therapy for the treatment of SMA by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Metabolomes were analyzed using targeted metabolomics utilizing 600 MHz 1H-NMR, parametric and nonparametric multivariate statistical analyses, machine learning, and modeling. Medical assessment before and after nusinersen therapy showed significant improvements of movement, posture, and strength according to various medical tests. No significant differences were found in metabolomes before and after nusinersen therapy in urine, serum, and liquor samples using an ensemble of statistical and machine learning approaches. In comparison to a healthy cohort, 1H-NMR metabolomes of SMA patients contained a reduced number and concentration of urine metabolites and differed significantly between males and females as well. Significantly larger data scatter was observed for SMA patients in comparison to matched healthy controls. Machine learning confirmed urinary creatinine as the most significant, distinguishing SMA patients from the healthy cohort. The positive effects of nusinersen therapy clearly preceded or took place devoid of significant rearrangements in the 1H-NMR metabolomic makeup of serum, urine, and liquor. Urine creatinine was successful at distinguishing SMA patients from the matched healthy cohort, which is a simple systemic novelty linking creatinine and SMA to the physiology of inactivity and diabetes, and it facilitates the monitoring of SMA disease in pediatric patients through non-invasive urine collection.

scholarly journals Are the Acute Effects of THC Different in Aging Adults?

2021 ◽  
Vol 11 (5) ◽  
pp. 590
Author(s):  
Raeghan L. Mueller ◽  
Jarrod M. Ellingson ◽  
L. Cinnamon Bidwell ◽  
Angela D. Bryan ◽  
Kent E. Hutchison
Keyword(s):  
Older Adults ◽  
Young Adults ◽  
Age Groups ◽  
Young Group ◽  
Self Administration ◽  
Behavioral Measures ◽  
Younger Adults ◽  
Different Types ◽  
Before And After ◽  
Aging Adults

In recent years of expanding legalization, older adults have reported the largest increase in cannabis use of any age group. While its use has been studied extensively in young adults, little is known about the effects of THC in older adults and whether the risks of cannabis might be different, particularly concerning intoxication and cognition. The current study investigated whether age is associated with the deleterious effects of THC on cognitive performance and other behavioral measures before and after ad libitum self-administration of three different types of cannabis flower (THC dominant, THC + CBD, and CBD dominant). Age groups consisted of young adults (ages 21–25) and older adults (ages 55–70). Controlling for pre-use scores on all measures, the THC dominant chemovar produced a greater deleterious effect in younger adults compared with older adults in tests of learning and processing speed, whereas there were no differences between old and young in the effects of the other chemovars. In addition, the young group reported greater cannabis craving than the older group after using the THC chemovar. Consistent with some reports in the preclinical literature, the findings suggest that older adults may be less sensitive to the effects of THC on cognitive and affective measures.

scholarly journals Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats

2006 ◽  
Vol 191 (2) ◽  
pp. 263-271 ◽  
Author(s):  
Wendy J. Lynch ◽  
Drew D. Kiraly ◽  
Barbara J. Caldarone ◽  
Marina R. Picciotto ◽  
Jane R. Taylor
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

Cyclosporine increases ischemia-induced endothelial progenitor cell mobilization through manipulation of the CD26 system

2008 ◽  
Vol 294 (3) ◽  
pp. R811-R818 ◽  
Author(s):  
Chao-Hung Wang ◽  
Wen-Jin Cherng ◽  
Ning-I Yang ◽  
Chia-Ming Hsu ◽  
Chi-Hsiao Yeh ◽  
...  
Keyword(s):  
Critical Role ◽  
Serum Levels ◽  
Blood Levels ◽  
Short Term ◽  
Endothelial Progenitor ◽  
Beneficial Effects ◽  
Dpp Iv ◽  
Before And After ◽  
Cell Mobilization

Cyclosporin A (CsA) improves the success rate of transplantation. The CD26/dipeptidylpeptidase IV (DPP IV) system plays a critical role in mobilizing endothelial progenitor cells (EPCs) from bone marrow. This study investigated whether CsA manipulates CD26/DPP IV activity and increases EPC mobilization. C57BL/6 mice were divided into control and CsA-treated groups. Before and after hindlimb ischemia was induced, circulating EPC number and serum levels of different cytokines were measured. Compared with the controls, CsA treatment significantly increased the blood levels of stroma-derived factor-1α and stem cell factor after ischemic stress ( P < 0.001). The CsA group displayed a significant increase in the number of circulating EPCs (sca-1+KDR+ and c-kit+CD31+ EPCs, both P < 0.05). In vivo, CsA caused a significant increase in the numbers of EPCs incorporated into the Matrigel and ischemic limbs ( P < 0.05). In the peripheral blood, CsA significantly decreased CD26+ cell numbers and attenuated the plasma CD26/DPP IV activity ( P < 0.001). Furthermore, short-term CsA treatment significantly improved the perfusion of ischemic limbs and decreased the spontaneous digital amputation rate. In summary, CsA manipulates the mobilization of EPCs into the circulation via the CD26/DPP IV system. Short-term CsA treatment has beneficial effects on angiogenesis of ischemic tissues.

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