Chronic treatment with antidepressant drugs reversibly alters NMDA mediated regulation of extracellular 5-HT in rat frontal cortex

Owen, Jenny C.E.; Whitton, Peter S.

doi:10.1016/j.brainresbull.2006.03.020

Cited by 12 publications

(4 citation statements)

References 23 publications

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“…Antagonism of the NR2B subunit of NMDA receptor proved to be effective in the clinics as recently demonstrated in a placebo-controlled, double-blind study with the compound CP-101606 (Preskorn et al, 2008). The blockade of NMDA receptors enhances the antidepressant efficacy of SSRIs in behavioral paradigms in rodents (Rogoz et al, 2002), which may, partly, be because of the activation of ascending serotonergic pathways onto the frontal cortex (Owen and Whitton, 2006). In humans, amantadine proved effective as an augmentation agent in treatmentresistant depression (Stryjer et al, 2003), and the interest of such a joint therapy with an antidepressant and amantadine has been confirmed more recently (Rogoz et al, 2007).…”

Section: Glutamatergic Approachmentioning

confidence: 94%

The pharmacological properties of antidepressants

Racagni¹,

Popoli

2010

International Clinical Psychopharmacology

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Antidepressant drugs represent one of the main forms of effective treatment for the amelioration of depressive symptoms. Most available antidepressants increase extracellular levels of monoamines. However, it is now recognized that monoamine levels and availability are only part of the story, and that antidepressants whose mechanism of action is mainly based on the modulation of monoaminergic systems may not be able to satisfy the unmet needs of depression. Therefore, a number of compounds, developed for their potential antidepressant activity, are endowed with putative mechanisms of action not affecting traditional monoamine targets. This article briefly reviews, within a mechanistic perspective, the pharmacological profiles of representative antidepressants from each class, including monoamine oxidase inhibitors, tricyclics, norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, norepinephrine and serotonin reuptake inhibitors, antidepressants interacting with dopaminergic, melatonergic, glutamatergic, or neuropeptide systems. The undesirable side effects of currently used antidepressants, which can often be a reason for lack of compliance, are also considered.

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Section: Glutamatergic Approachmentioning

confidence: 94%

The pharmacological properties of antidepressants

Racagni¹,

Popoli

2010

International Clinical Psychopharmacology

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“…60 Using direct brain serotonin measuring techniques and injecting a glutamate-blocker directly into rodent amygdala, animal models have confirmed that increasing serotonin with a glutamate-blockade will rapidly resolve anxiety symptoms. 61,62 Decreasing glutamate via enhanced serotonin is beneficial to anxiety disorders. Methadone has proven to increase serotonin and can be expected to decrease glutamate on that basis.…”

Section: Glutamate Excessmentioning

confidence: 99%

Psychotherapeutic Benefits of Opioid Agonist Therapy

Tenore

2008

Journal of Addictive Diseases

119

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Opioids have been used for centuries to treat a variety of psychiatric conditions with much success. The so-called "opium cure" lost popularity in the early 1950s with the development of non-addictive tricyclic antidepressants and monoamine oxidase inhibitors. Nonetheless, recent literature supports the potent role of methadone, buprenorphine, tramadol, morphine, and other opioids as effective, durable, and rapid therapeutic agents for anxiety and depression. This article reviews the medical literature on the treatment of psychiatric disorders with opioids (notably, methadone and buprenorphine) in both the non-opioid-dependent population and in the opioid-dependent methadone maintenance population. The most recent neurotransmitter theories on the origin of depression and anxiety will be reviewed, including current information on the role of serotonin, N-Methyl d-Aspartate, glutamate, cortisol, catecholamine, and dopamine in psychiatric disorders. The observation that methadone maintenance patients with co-existing psychiatric morbidity (so called dual diagnosis patients) require substantially higher methadone dosages by between 20% and 50% will be explored and qualified. The role of methadone and other opioids as beneficial psychiatric medications that are independent of their drug abuse mitigating properties will be discussed. The mechanisms by which methadone and other opioids can favorably modulate the neurotransmitter systems controlling mood will also be discussed.

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“…The mechanisms underlying the therapeutic actions of SSRIs are still subject to considerable debate [59][60][61]. Of special interest is the delay between the pharmacologic effects of SSRIs, which occur as soon as the brain is exposed to the drug, and the therapeutic effects, which can take weeks.…”

Section: Future Directions I Chronic Sert Inhibition -Modeling Ssri mentioning

confidence: 99%

The mechanisms of serotonergic signaling in Drosophila

Borue¹

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Serotonin signaling plays a key role in the regulation of development, mood and behavior. Selective serotonin reuptake inhibitors (SSRIs) have been the standard of treatment for several mental disorders, including depression. However, our understanding of their effects is incomplete and the serotonergic system in mammals is complex, making it difficult to study. Drosophila is well suited for the study of the basic mechanisms of serotonergic signaling, but the small size of its nervous system has previously precluded the direct measurements of neurotransmitters. We have developed a novel combination of methods to study serotonergic signaling in the larval Drosophila central nervous system. Fast-scan cyclic voltammetry at inserted microelectrodes is used to detect serotonin elicited by channelrhodopsin-2 (ChR2) mediated depolarization. This dissertation demonstrates the first real-time measurements of serotonin dynamics in a single larval Drosophila nerve cord. A characterization of serotonin release and clearance in the fly, including the estimation of Michaelis-Menten constants, shows that they are analogous to those in mammals, making this simple organism more useful for the study of the basic physiological mechanisms of serotonergic signaling. The effects of pharmacologically inhibiting serotonin synthesis or reuptake on the releasable pool of serotonin are probed with multiple stimulation experiments. Reuptake is shown to be important for the clearance of serotonin from the extracellular space as well as the rapid replenishment of the releasable pool. Synthesis is critical to the longerterm replenishment of the releasable pool, especially when reuptake is concurrently inhibited. Decreases in serotonin are rescued by inhibiting action potential propagation with tetrodotoxin, implicating endogenous activity in depletion of neuronal serotonin. These results give insight into the possible effects of SSRIs on the serotonergic system and the important role that synthesis may play in this phenomenon as well as in overall serotonergic neuron function. The have also paved the way for future use of Drosophila for large-scale genetic analysis of neurotransmitter dynamics. This dissertation was completed under the direction of Jill Venton, PhD, in the Department of Chemistry and Neuroscience Graduate Program.

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Chronic treatment with antidepressant drugs reversibly alters NMDA mediated regulation of extracellular 5-HT in rat frontal cortex

Cited by 12 publications

References 23 publications

The pharmacological properties of antidepressants

The pharmacological properties of antidepressants

Psychotherapeutic Benefits of Opioid Agonist Therapy

The mechanisms of serotonergic signaling in Drosophila

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