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 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 Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA

2013 ◽  
Vol 16 (6) ◽  
pp. 1383-1394 ◽  
Author(s):  
Tori L. Schaefer ◽  
Curtis E. Grace ◽  
Amanda A. Braun ◽  
Robyn M. Amos-Kroohs ◽  
Devon L. Graham ◽  
...  
Keyword(s):  
Brain Development ◽  
Cognitive Deficits ◽  
System Development ◽  
Third Trimester ◽  
Learning Deficits ◽  
Developmental Exposure ◽  
Target Field ◽  
Field Organization ◽  
Serotonergic Drugs

Abstract We previously showed that developmental 3,4-methylenedioxymethamphetamine (MDMA) treatment induces long-term spatial and egocentric learning and memory deficits and serotonin (5-HT) reductions. During brain development, 5-HT is a neurotrophic factor influencing neurogenesis, synaptogenesis, migration, and target field organization. MDMA (10 mg/kg × 4/d at 2 h intervals) given on post-natal day (PD) 11–20 in rats (a period of limbic system development that approximates human third trimester brain development) induces 50% reductions in 5-HT during treatment and 20% reductions when assessed as adults. To determine whether the 5-HT reduction is responsible for the cognitive deficits, we used citalopram (Cit) pretreatment to inhibit the effects of MDMA on 5-HT reuptake in a companion study. Cit attenuated MDMA-induced 5-HT reductions by 50% (Schaefer et al., 2012). Here we tested whether Cit (5 or 7.5 mg/kg × 2/d) pretreatment attenuates the cognitive effects of MDMA. Within each litter, different offspring were treated on PD11–20 with saline (Sal) + MDMA, Cit + MDMA, Cit + Sal or Sal + Sal. Neither spatial nor egocentric learning/memory was improved by Cit pretreatment. Unexpectedly, Cit + Sal (at both doses) produced spatial and egocentric learning deficits as severe as those caused by Sal + MDMA. These are the first data showing cognitive deficits resulting from developmental exposure to a selective serotonin reuptake inhibitor. These data indicate the need for further research on the long-term safety of antidepressants during pregnancy.

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.

Aging-related changes in brain metabolism are altered by early developmental exposure to diazepam

1990 ◽  
Vol 11 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Rajesh Miranda ◽  
Toni Ceckler ◽  
Ronnie Guillet ◽  
Carol K. Kellogg
Keyword(s):  
Brain Metabolism ◽  
Developmental Exposure ◽  
Early Developmental

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.

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