Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry

Kalia, Madhu; O’Callaghan, James P.; Miller, Diane B.; Kramer, Michael

doi:10.1016/s0006-8993(99)02430-0

Cited by 19 publications

(14 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are only aware of one study that has tested whether antidepressants cause structural damage to neurons (Kalia et al, 2000). The study authors found that exposure to clinically relevant doses of fluoxetine (11.4 mg/kg, oral) or sertraline (28.6 mg/kg, oral) for only 4 days caused shortened axons, kinks, and swollen nerve terminals in the brains of otherwise healthy rodents.…”

Section: Increased Risk Of Relapse After Antidepressant Discontinuationmentioning

confidence: 99%

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

Andrews¹,

Thomson²,

Amstadter³

et al. 2012

Front. Psychology

106

View full text Add to dashboard Cite

Antidepressant medications are the first-line treatment for people meeting current diagnostic criteria for major depressive disorder. Most antidepressants are designed to perturb the mechanisms that regulate the neurotransmitter serotonin – an evolutionarily ancient biochemical found in plants, animals, and fungi. Many adaptive processes evolved to be regulated by serotonin, including emotion, development, neuronal growth and death, platelet activation and the clotting process, attention, electrolyte balance, and reproduction. It is a principle of evolutionary medicine that the disruption of evolved adaptations will degrade biological functioning. Because serotonin regulates many adaptive processes, antidepressants could have many adverse health effects. For instance, while antidepressants are modestly effective in reducing depressive symptoms, they increase the brain’s susceptibility to future episodes after they have been discontinued. Contrary to a widely held belief in psychiatry, studies that purport to show that antidepressants promote neurogenesis are flawed because they all use a method that cannot, by itself, distinguish between neurogenesis and neuronal death. In fact, antidepressants cause neuronal damage and mature neurons to revert to an immature state, both of which may explain why antidepressants also cause neurons to undergo apoptosis (programmed death). Antidepressants can also cause developmental problems, they have adverse effects on sexual and romantic life, and they increase the risk of hyponatremia (low sodium in the blood plasma), bleeding, stroke, and death in the elderly. Our review supports the conclusion that antidepressants generally do more harm than good by disrupting a number of adaptive processes regulated by serotonin. However, there may be specific conditions for which their use is warranted (e.g., cancer, recovery from stroke). We conclude that altered informed consent practices and greater caution in the prescription of antidepressants are warranted.

show abstract

Section: Increased Risk Of Relapse After Antidepressant Discontinuationmentioning

confidence: 99%

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

Andrews¹,

Thomson²,

Amstadter³

et al. 2012

Front. Psychology

106

View full text Add to dashboard Cite

show abstract

“…Chronic administration of 5-HT selective reuptake inhibitors (SSRIs), like paroxetine and sertraline, leads to a marked loss of SERT binding and function comparable to MDMA, but these agents are therapeutic drugs rather than neurotoxins (Benmansour et al 1999; Frazer and Benmansour 2002). Finally, high-dose administration of SSRIs produces swollen, fragmented, and abnormal 5-HT terminals, which are indistinguishable from the effects of MDMA and other substituted amphetamines (Kalia et al 2000). …”

Section: Effects Of Mdma On Monoamine Neuronsmentioning

confidence: 99%

3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings

2006

View full text Add to dashboard Cite

Rationale3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug. In animals, high-dose administration of MDMA produces deficits in serotonin (5-HT) neurons (e.g., depletion of forebrain 5-HT) that have been interpreted as neurotoxicity. Whether such 5-HT deficits reflect neuronal damage is a matter of ongoing debate.ObjectiveThe present paper reviews four specific issues related to the hypothesis of MDMA neurotoxicity in rats: (1) the effects of MDMA on monoamine neurons, (2) the use of “interspecies scaling” to adjust MDMA doses across species, (3) the effects of MDMA on established markers of neuronal damage, and (4) functional impairments associated with MDMA-induced 5-HT depletions.ResultsMDMA is a substrate for monoamine transporters, and stimulated release of 5-HT, NE, and DA mediates effects of the drug. MDMA produces neurochemical, endocrine, and behavioral actions in rats and humans at equivalent doses (e.g., 1–2 mg/kg), suggesting that there is no reason to adjust doses between these species. Typical doses of MDMA causing long-term 5-HT depletions in rats (e.g., 10–20 mg/kg) do not reliably increase markers of neurotoxic damage such as cell death, silver staining, or reactive gliosis. MDMA-induced 5-HT depletions are accompanied by a number of functional consequences including reductions in evoked 5-HT release and changes in hormone secretion. Perhaps more importantly, administration of MDMA to rats induces persistent anxiety-like behaviors in the absence of measurable 5-HT deficits.ConclusionsMDMA-induced 5-HT depletions are not necessarily synonymous with neurotoxic damage. However, doses of MDMA which do not cause long-term 5-HT depletions can have protracted effects on behavior, suggesting even moderate doses of the drug may pose risks.

show abstract

“…In addition, neurotransmitter immunohistochemistry may augment the interpretation of other biochemical data. This approach has been applied to neurotoxicity evaluations that characterize the loss of serotonin immunoreactivity in adult rats after treatment with drugs known to act on this neurotransmitter system (34,35). These studies have shown not only the loss of serotonin immunoreactivity but also changes in the morphologic appearance of the serotonin nerve terminal network.…”

Section: Stains For Neurotransmitters and Neuron-specific Protein Marmentioning

confidence: 99%

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology.

Garman¹,

Fix²,

Jortner³

et al. 2001

Environ Health Perspect

View full text Add to dashboard Cite

Neuropathologic assessment of chemically induced developmental alterations in the nervous system for regulatory purposes is a multifactorial, complex process. This calls for careful qualitative and quantitative morphologic study of numerous brains at several developmental stages in rats. Quantitative evaluation may include such basic methods as determination of brain weight and dimensions as well as the progressively more complex approaches of linear, areal, or stereologic measurement of brain sections. Histologic evaluation employs routine stains (such as hematoxylin and eosin), which can be complemented by a variety of special and immunohistochemical procedures. These brain studies are augmented by morphologic assessment of selected peripheral nervous system structures. Studies of this nature require a high level of technical skill as well as special training on the part of the pathologist. The pathologist should have knowledge of normal microscopic neuroanatomy/neuronal circuitry and an understanding of basic principles of developmental neurobiology, such as familiarity with the patterns of physiologic or programmed cell de

show abstract

Comparative study of fluoxetine, sibutramine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry

Cited by 19 publications

References 32 publications

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

Primum Non Nocere: An Evolutionary Analysis of Whether Antidepressants Do More Harm than Good

3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. II: neuropathology.

Contact Info

Product

Resources

About