scholarly journals Tianeptine, but not fluoxetine, decreases avoidant behavior in a mouse model of early developmental exposure to fluoxetine

2021 ◽  
Author(s):  
Elizabeth A Pekarskaya ◽  
Emma S Holt ◽  
Jay A Gingrich ◽  
Mark S Ansorge ◽  
Jonathan A Javitch ◽  
...  
Keyword(s):  
Open Field ◽  
Alternative Treatment ◽  
Chronic Administration ◽  
Therapeutic Effects ◽  
Pharmacological Agents ◽  
Disease Etiology ◽  
Promising Alternative ◽  
Alternative Treatment Strategy ◽  
Baseline Testing ◽  
Avoidant Behavior

ABSTRACTDepression and anxiety are two of the most common mental health disorders, often sharing symptoms and administrations. Most pharmacological agents available to treat these disorders target monoamine systems. Currently, finding the most effective treatment for an individual is a process of trial and error. Therefore, to better understand how disease etiology may predict treatment response, we studied mice exposed developmentally to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX). These mice show the murine equivalent of anxiety- and depression-like symptoms in adulthood and here we report that these mice are also behaviorally resistant to the antidepressant-like effects of adult SSRI administration. We investigated whether tianeptine (TIA), which exerts its therapeutic effects through the mu-opioid receptor (MOR) instead of directly targeting monoaminergic systems, would be more effective in this model.We injected C57BL/6J (C57) pups with either FLX (10 mg/kg, i.p) or vehicle from postnatal (PN) day 2 to 11, a period in which mouse brain development parallels that of the third trimester of a human pregnancy. Prior work established that adult 129SvEv (129) mice exposed to FLX in this time period (PN-FLX) showed increased avoidant and decreased hedonic behaviors, which correspond to anxiety- and depressive-like symptoms in humans, respectively. We performed baseline testing in adulthood in C57 PN-FLX animals and confirmed a similar avoidant phenotype to that reported in 129 PN-FLX mice. We then treated these animals with chronic FLX (18 mg/kg in the drinking water) and evaluated effects on two tasks that measure avoidant behavior – the open field and novelty suppressed feeding (NSF) tasks. This administration failed to improve, and even exacerbated, avoidance symptoms in PN-FLX mice. The same animals then underwent chronic administration with TIA (30 mg/kg, 2x/day, i.p.) as an alternative treatment strategy. TIA administration decreased avoidance behavior as measured in the open field and NSF. Overall, this demonstrates that TIA may be a promising alternative treatment to typical antidepressants, especially in patients whose serotonergic system has been altered.

scholarly journals Tianeptine, but not fluoxetine, decreases avoidant behavior in a mouse model of early developmental exposure to fluoxetine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elizabeth A. Pekarskaya ◽  
Emma S. Holt ◽  
Jay A. Gingrich ◽  
Mark S. Ansorge ◽  
Jonathan A. Javitch ◽  
...  
Keyword(s):  
Therapeutic Effects ◽  
Depression And Anxiety ◽  
Third Trimester ◽  
Pharmacological Agents ◽  
Disease Etiology ◽  
Promising Alternative ◽  
Developmental Exposure ◽  
Early Developmental ◽  
Ssri Treatment ◽  
Predict Treatment Response

AbstractDepression and anxiety, two of the most common mental health disorders, share common symptoms and treatments. Most pharmacological agents available to treat these disorders target monoamine systems. Currently, finding the most effective treatment for an individual is a process of trial and error. To better understand how disease etiology may predict treatment response, we studied mice exposed developmentally to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX). These mice show the murine equivalent of anxiety- and depression-like symptoms in adulthood and here we report that these mice are also behaviorally resistant to the antidepressant-like effects of adult SSRI administration. We investigated whether tianeptine (TIA), which exerts its therapeutic effects through agonism of the mu-opioid receptor instead of targeting monoaminergic systems, would be more effective in this model. We found that C57BL/6J pups exposed to FLX from postnatal day 2 to 11 (PNFLX, the mouse equivalent in terms of brain development to the human third trimester) showed increased avoidant behaviors as adults that failed to improve, or were even exacerbated, by chronic SSRI treatment. By contrast, avoidant behaviors in these same mice were drastically improved following chronic treatment with TIA. Overall, this demonstrates that TIA may be a promising alternative treatment for patients that fail to respond to typical antidepressants, especially in patients whose serotonergic system has been altered by in utero exposure to SSRIs.

scholarly journals Monoaminergic Involvement in Decreased Locomotor Activity of Mice Treated with α and β-amyrin from Protium heptaphyllum

2018 ◽  
Vol 13 (8) ◽  
pp. 1934578X1801300
Author(s):  
Gislei F. Aragão ◽  
Manoel O. de Moraes Filho ◽  
Paulo N. Bandeira ◽  
Antônio P. Frota Junior ◽  
Yasmin Ingrid S. Oliveira de ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Locomotor Activity ◽  
Open Field ◽  
Field Test ◽  
High Performance ◽  
Open Field Test ◽  
Inhibitory Effect ◽  
Pharmacological Agents ◽  
Tissue Homogenates ◽  
The Central Nervous System

A triterpenic mixture of α and β-amyrin (AMY) extracted from Protium heptaphyllum has demonstrated several pharmacological effects, including activity in the central nervous system. The aim of this study was to evaluate the effect of AMY administration on locomotor activity of mice by the open field test using some monoaminergic agonists and antagonists and the cerebral cortex levels of monoamines and their major metabolites by high-performance liquid chromatography. Mice were treated acutely with AMY at doses of 1, 2.5 and 5 mg/kg given intraperitoneally and with the pharmacological agents and placed in open field test, then the animals were sacrificed and the cerebral cortex extracted, and monoamines were assayed in tissue homogenates. AMY at 1, 2.5 and 5 mg/kg decreased locomotor activity of animals by 25, 31 and 39%, respectively in the open field test. Ondasentron, doxazosin, oxymetazoline and clonidine did not reverse the inhibitory effect of 5 mg/kg AMY. Venlafaxine and yohimbine reversed the inhibitory effect of 5 mg AMY. In the cortex, the 5-HT and 5-HIAA were significantly reduced by the administration of AMY. NE and HVA were also reduced with 2.5 and 5 mg/kg AMY, while Dopamine and DOPAC were not increased with AMY. In conclusion, AMY decreased locomotor activity of animals accompanied by a decrease in 5-HT and NE levels in the cerebral cortex, this locomotor effect is reversed by drug that blocker the α-2-adrenoreceptor.

Effect of tianeptine on neuroendocrine, enzyme and behavioral responses to restraint stress in male rats

1993 ◽  
Vol 8 (S2) ◽  
pp. 67s-73s ◽  
Author(s):  
R Fontanges ◽  
J Mimouni ◽  
X de Grieve ◽  
J Picard ◽  
M Pugeat ◽  
...  
Keyword(s):  
Open Field ◽  
Restraint Stress ◽  
Wistar Rats ◽  
Chronic Treatment ◽  
Single Injection ◽  
Behavioral Responses ◽  
Chronic Administration ◽  
Exploratory Activity ◽  
Male Rats ◽  
The Novel

SummaryThe effects of the novel antidepressant tianeptine, after acute or chronic administration, were compared in normal and restraint-stressed (30 min or 2 h) Wistar rats. Tianeptine, at the dose of 10 mg/kg, did not exert any effect in non-stressed rats. However, in animals restrained for 30 min, tianeptine reduced the increase of circulating ACTH and β-endorphin levels without modification of corticosterone. Moreover, it antagonized the deficit of vertical exploratory activity in an open field. In rats restrained for 2 hours, a single injection of tianeptine suppressed the stress-induced increase of TAT hepatic activity and moderately attenuated the deficit of activity in the open field. This effect was less marked and not statistically significant after chronic treatment.

Influence of nicotine on the core temperature response to a novel environment in pregnant rats

1997 ◽  
Vol 83 (5) ◽  
pp. 1612-1616 ◽  
Author(s):  
James E. Fewell ◽  
Patricia A. Tang
Keyword(s):  
Open Field ◽  
Core Temperature ◽  
Temperature Response ◽  
Chronic Administration ◽  
Female Rat ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Temperature Index ◽  
Novel Environment ◽  
The Core

Fewell, James E., and Patricia A. Tang. Influence of nicotine on the core temperature response to a novel environment in pregnant rats. J. Appl. Physiol.83(5): 1612–1616, 1997.—Exposure of a male or nonpregnant female rat to a novel environment, such as a simulated open field, induces a transient increase in core temperature, which is often called stress-induced hyperthermia. Pregnancy alters this response such that the core temperature index increases significantly during exposure to a simulated open field on day 10 but not on days 15 and 20 of gestation in rats. The present experiments were carried to investigate the effect of chronic administration of nicotine (0, 1, 2, 4, or 8 mg ⋅ kg−1 ⋅ 24 h−1 for 13–15 days) on the core temperature response to a simulated open field in chronically instrumented pregnant ( day 20 or 21 of gestation) and nonpregnant Sprague-Dawley rats. In nonpregnant rats, the core temperature index increased more during exposure to a simulated open field after chronic administration of nicotine at all doses than after chronic administration of vehicle; the core temperature response was not dependent on the dose of nicotine. In pregnant rats, significant increases in core temperature as well as in the core temperature index occurred only during exposure to a simulated open field after chronic administration of nicotine in doses of 2, 4, or 8 mg ⋅ kg−1 ⋅ 24 h−1; the core temperature response was dependent on the dose of nicotine. Our data provide evidence that chronic exposure to nicotine enhances the core temperature response to a simulated open field in nonpregnant rats and unmasks a maternal thermogenic response that is not seen to the same stimulus near term of pregnancy. The possible physiological consequences for the fetus are presently unknown and require investigation.

Neurobiological mechanisms of repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex in depression: a systematic review

2015 ◽  
Vol 45 (16) ◽  
pp. 3411-3432 ◽  
Author(s):  
Y. Noda ◽  
W. K. Silverstein ◽  
M. S. Barr ◽  
F. Vila-Rodriguez ◽  
J. Downar ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Treatment Resistance ◽  
Mental Illnesses ◽  
Antidepressant Effect ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Exclusion Criteria ◽  
Promising Alternative

Depression is one of the most prevalent mental illnesses worldwide and a leading cause of disability, especially in the setting of treatment resistance. In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative strategy for treatment-resistant depression and its clinical efficacy has been investigated intensively across the world. However, the underlying neurobiological mechanisms of the antidepressant effect of rTMS are still not fully understood. This review aims to systematically synthesize the literature on the neurobiological mechanisms of treatment response to rTMS in patients with depression. Medline (1996–2014), Embase (1980–2014) and PsycINFO (1806–2014) were searched under set terms. Three authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Of 1647 articles identified, 66 studies met both inclusion and exclusion criteria. rTMS affects various biological factors that can be measured by current biological techniques. Although a number of studies have explored the neurobiological mechanisms of rTMS, a large variety of rTMS protocols and parameters limits the ability to synthesize these findings into a coherent understanding. However, a convergence of findings suggest that rTMS exerts its therapeutic effects by altering levels of various neurochemicals, electrophysiology as well as blood flow and activity in the brain in a frequency-dependent manner. More research is needed to delineate the neurobiological mechanisms of the antidepressant effect of rTMS. The incorporation of biological assessments into future rTMS clinical trials will help in this regard.

scholarly journals Pathophysiology of Ganglioside GM1 in Ischemic Stroke: Ganglioside GM1: A Critical Review

2019 ◽  
Vol 28 (6) ◽  
pp. 657-661 ◽  
Author(s):  
Wenchao Zhang ◽  
Paul R. Krafft ◽  
Tianlong Wang ◽  
John H. Zhang ◽  
Li Li ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Critical Review ◽  
Neurological Diseases ◽  
Therapeutic Effects ◽  
Ganglioside Gm1 ◽  
Promising Alternative ◽  
Ischemic Brain ◽  
Stroke Treatment ◽  
The Past ◽  
Cerebral Ischemic

Ganglioside GM1 is a member of the ganglioside family which has been used in many countries and is thought of as a promising alternative treatment for preventing several neurological diseases, including cerebral ischemic injury. The therapeutic effects of GM1 have been proved both in neonates and in adults following ischemic brain damage; however, its clinical efficacy in patients with ischemic stroke is still uncertain. This review examines the recent knowledge of the neuroprotective properties of GM1 in ischemic stroke, collected in the past two decades. We conclude that GM1 may have potential for stroke treatment, although we need to be cautious in respect of its complications.

scholarly journals Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic

2020 ◽  
Vol 319 (6) ◽  
pp. L941-L948 ◽  
Author(s):  
León Ferder ◽  
Virna Margarita Martín Giménez ◽  
Felipe Inserra ◽  
Carlos Tajer ◽  
Laura Antonietti ◽  
...  
Keyword(s):  
Public Health ◽  
Vitamin D ◽  
Severe Acute Respiratory Syndrome ◽  
Renin Angiotensin System ◽  
Vitamin D Supplementation ◽  
Therapeutic Effects ◽  
Pharmacological Agents ◽  
Angiotensin System ◽  
Therapeutic Measure ◽  
Oxidative Signaling

The COVID-19 pandemic has reached most of the countries worldwide causing death, which often results from an inflammatory storm associated with severe acute respiratory syndrome (SARS). This has prompted researchers to seek specific novel and definitive treatments urgently. In this context, it is interesting to evaluate the preventive and therapeutic effects of existing pharmacological agents that could be useful. In this regard, vitamin D supplementation, particularly in individuals likely to be deficient, may be a promising option. Vitamin D is a hormone that modulates many of the same inflammatory and oxidative signaling pathways triggered during COVID-19. For example, vitamin D suppresses the actions of the renin-angiotensin system, which has a determining role in the pathophysiology of the inflammatory response related to COVID-19. This paper analyzes the evidence that vitamin D supplementation might be a valuable preventive/therapeutic measure in groups at risk for or infected with COVID-19. It also discusses how clinical studies could be best designed to evaluate the possible advantages of vitamin D supplementation for the benefit of public health during the pandemic.

scholarly journals Electrophysiological biomarkers of neuromodulatory strategies to recover motor function after spinal cord injury

2015 ◽  
Vol 113 (9) ◽  
pp. 3386-3396 ◽  
Author(s):  
Parag Gad ◽  
Roland R. Roy ◽  
Jaehoon Choe ◽  
Jack Creagmile ◽  
Hui Zhong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Control ◽  
Evoked Potentials ◽  
Motor Performance ◽  
Weight Bearing ◽  
Chronic Administration ◽  
Pharmacological Agents ◽  
Extensor Muscles ◽  
Cord Injury ◽  
Complete Paralysis

The spinal cord contains the circuitry to control posture and locomotion after complete paralysis, and this circuitry can be enabled with epidural stimulation [electrical enabling motor control (eEmc)] and/or administration of pharmacological agents [pharmacological enabling motor control (fEmc)] when combined with motor training. We hypothesized that the characteristics of the spinally evoked potentials after chronic administration of both strychnine and quipazine under the influence of eEmc during standing and stepping can be used as biomarkers to predict successful motor performance. To test this hypothesis we trained rats to step bipedally for 7 wk after paralysis and characterized the motor potentials evoked in the soleus and tibialis anterior (TA) muscles with the rats in a non-weight-bearing position, standing and stepping. The middle responses (MRs) to spinally evoked stimuli were suppressed with either or both drugs when the rat was suspended, whereas the addition of either or both drugs resulted in an overall activation of the extensor muscles during stepping and/or standing and reduced the drag duration and cocontraction between the TA and soleus muscles during stepping. The administration of quipazine and strychnine in concert with eEmc and step training after injury resulted in larger-amplitude evoked potentials [MRs and late responses (LRs)] in flexors and extensors, with the LRs consisting of a more normal bursting pattern, i.e., randomly generated action potentials within the bursts. This pattern was linked to more successful standing and stepping. Thus it appears that selected features of the patterns of potentials evoked in specific muscles with stimulation can serve as effective biomarkers and predictors of motor performance.

Engraftment Kinetics After Transplantation of Double Units of Umbilical Cord Blood From Unrelated Donors in Adolescents and Adults with Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1183-1183 ◽  
Author(s):  
Miao Zhou ◽  
Zimin Sun ◽  
Huilan Liu ◽  
Liangquan Geng ◽  
Xingbing Wang ◽  
...  
Keyword(s):  
High Risk ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Hematologic Malignancies ◽  
Therapeutic Effects ◽  
Promising Alternative ◽  
Cell Dose ◽  
The One

Abstract Abstract 1183 Poster Board I-205 Objective: To evaluate the clinical therapeutic effects and the early engraftment kinetics of the transplantation of double partially-human leukocyte antigen (HLA)-matched umbilical cord blood (UCB) units in patients with hematologic malignancies from November 2005 to March 2009. Methods: Twenty-one adults and adolescents (median age 21 years [range 10-40 years]; median weight 57 kg [range 31-76 kg]; 16 males and 5 females) with hematologic malignancies were given transplants of double UCB units. Diagnoses included 7 ALL patients, 7 AML, 5 CML, 1 Mix-AL, and 1MDS. 17 (81%) of the patients were refractory to chemotherapy and considered at high risk. All patients received myeloablative conditioning, which included Flu/Cy/TBI for 16 patients, and Bu/CY2±ATG±Ara-C for 5 patients. Graft versus host disease (GVHD) prophylaxis was CSA+MMF. The analytic method used was based on the quantitative amplification of informative polymorphic short tandem repeat (STR) regions in the recipient and donor using polymerase chain reaction (PCR), which detect engraftment and chimerism dynamically. Results: The median nucleated cell dose was 4.93×107 nucleated cell [NC]/kg range:3.26-7.70×107 NC/kg. Eighteen patients (86%) achieved hematopoietic recovery after the double UCB transplantation. The median number of days required to reach an ANC > 0.5×109/L was 20 days (14–35 days), and platelet> 20×109/L was 34.5 days (25 - 49 days). One patient's engraftment was derived from both donors, which were 6/6 HLA matched the recipient's, for six months until her death. The other 17 patients achieved sustained hematopoietic engraftment that was derived from a single dominant donor based on STR-PCR results. The median infused cell dose of the engrafted units was 2.34×107 NC /Kg (ranging from 1.87 to 4.45 ×107NC/kg), and 3.225×107CD3+/Kg (ranging from 0.51 to 13.92×107 CD3+/kg). This compared with 2.17×107 NC/Kg (range: 0.96 - 3.98×107 NC/kg) and 1.71×107CD3+/Kg (range: 0.40 - 10.65×107 CD3+/kg) in the nonsustained unit. The difference in cell doses was not significant(P=0.718 AP=0.073. By STR-PCR, the donor DNA can be detected as early as post-transplantational day 7. Seventeen patients who achieved dominant engraftment had full donor chimera (FDC) at post-transplantational day 14, and this was highly consistency with chimerisms at post-transplantational days 21 and 30. If no unit reached FDC at post-transplantational day 14, the graft would be rejected. Therefore, the result at post-transplantational day 14 could indicate the last chimerism (Kappa =1). Complications: 1) Three patients had UCB graft rejections at early period; two were adolescent ALL, one was MDS-RCMD. Depending on long-term transfusion, they all achieved long-term hematopoiesis recovery after a secondary haploidentical stem cell transplantation at post-DUCBT 33-38 day. 2) Eight/eighteen patients(44.4%)had grade±-IIacute GVHD, 2 in accessible 13 patients developed local (non-extensive) cGVHD. 3) Three patients relapsed (1 was CNSL, and 1 relapsed on cellular level and re-achieved FDC after treatment with imatinib and benzene). 4) All patients had a median follow-up of 12 months (ranging 5 months to 43 months). The one-year disease-free survival rate was 66.64%, with 6 patients died. The one hundred-day transplantation-related mortality was 14.3%; 4 died of invasive fungal infection, 1 died of body exhaustion, and 1 died of serious hepatitis. Conclusion: 1) Double-unit UCB can overcome the shortage of cell dose in one-unit UCB, and was proved to be a safe, effective, and promising alternative treatment option with good engraftment potential. 2) The total nucleated cells and CD3 cell dose were not associated with the UCB unit that would predominate. 3) The STR -PCR and capillary electrophoresis techniques can accurately evaluate grafting at an early time after UCBT. Detecting the chimerism at 14 days after UCBT can provide the information on graft implantation. 4) The relapse rate was 14.3% in 18 CB-engrafted patients with high-risk and refractory disease conditions, which suggests that UCBT has a fairly good graft versus leukemia effect. Disclosures: No relevant conflicts of interest to declare.

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