Evaluation of 5-HT2A and mGlu2/3 receptors in postmortem prefrontal cortex of subjects with major depressive disorder: Effect of antidepressant treatment

Muguruza, Carolina; Miranda-Azpiazu, Patrícia; Dı́ez-Alarcia, Rebeca; Morentín, Benito; González-Maeso, Javier; Callado, Luís F.; Meana, J. Javier

doi:10.1016/j.neuropharm.2014.08.009

Cited by 65 publications

(41 citation statements)

References 55 publications

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“…There is anecdotal evidence that psychedelic effects are largely attenuated by ongoing treatment with SSRIs (Bonson, Buckholtz & Murphy, 1996) and perhaps with other antidepressants . Down-regulation of 5-HT2A receptors is a feature of many different first-line antidepressant drugs (Muguruza et al, 2014), as well as second-line antidepressant medications (e.g. atypical antipsychotics) with significant 5-HT2AR antagonist properties (Gray & Roth, 2001).…”

Section: "All Who Drink Of This Remedy Recover In a Short Time Excepmentioning

confidence: 99%

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

Carhart‐Harris

Goodwin

2017

Neuropsychopharmacol

461

320

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Plant-based psychedelics such as psilocybin have an ancient history of medicinal use. After the first English-language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aides to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programmes. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and 3 separate clinical trials of psilocybin for depressive symptoms. In this Circumspective piece, Robin Carhart-Harris and Guy Goodwin share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.The therapeutic potential of psychedelic drugs: tempered optimism (Robin CarhartHarris)

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Section: "All Who Drink Of This Remedy Recover In a Short Time Excepmentioning

confidence: 99%

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

Carhart‐Harris

Goodwin

2017

Neuropsychopharmacol

461

320

View full text Add to dashboard Cite

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“…In line with our gene expression data, decreased hippocampal 5‐HT 2A receptor densities have been reported in [ 3 H]ketanserine binding experiments ( post‐mortem ) and PET studies with MDD patients (Cheetham, Crompton, Katona, & Horton, ; Rosel, Arranz, Vallejo, Oros, Crespo, Menchon, & Navarro, ; Rosel, Arranz, San, Vallejo, Crespo, Urretavizcaya, & Navarro, ; Mintun, Sheline, Moerlein, Vlassenko, Huang, & Snyder, ; Sheline, Mintun, Barch, Wilkins, Snyder, & Moerlein, ). In the frontal cortex of depressed suicide victims, results are mixed with two studies (Arranz, Eriksson, Mellerup, Plenge, & Marcusson, ; Muguruza, Miranda‐Azpiazu, Díez‐Alarcia, Morentin, González‐Maeso, Callado, & Meana, ) showing no difference in 5‐HT 2A receptor binding and two reporting increased binding (Hrdina, Demeter, Vu, Sótónyi, & Palkovits, ; Shelton, Sanders‐Bush, Manier, & Lewis, ). Since SSRI treatment has been reported to affect 5‐HT 2A receptor expression (Muguruza et al, ), this discrepancy may be related to differences in antidepressant treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In the frontal cortex of depressed suicide victims, results are mixed with two studies (Arranz, Eriksson, Mellerup, Plenge, & Marcusson, ; Muguruza, Miranda‐Azpiazu, Díez‐Alarcia, Morentin, González‐Maeso, Callado, & Meana, ) showing no difference in 5‐HT 2A receptor binding and two reporting increased binding (Hrdina, Demeter, Vu, Sótónyi, & Palkovits, ; Shelton, Sanders‐Bush, Manier, & Lewis, ). Since SSRI treatment has been reported to affect 5‐HT 2A receptor expression (Muguruza et al, ), this discrepancy may be related to differences in antidepressant treatment. On transcript level, one recent study assessing 5‐HT 2A expression in the prefrontal cortex did not detect any differences between deceased MDD patients and control subjects (Muguruza et al, ).…”

Section: Discussionmentioning

confidence: 99%

Gene expression related to serotonergic and glutamatergic neurotransmission is altered in the flinders sensitive line rat model of depression: Effect of ketamine

Jardin

Müller

Sanchéz

et al. 2016

Synapse

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Major depressive disorder (MDD) is associated with dysfunctional serotonergic and glutamatergic neurotransmission, and the genetic animal model of depression Flinders Sensitive Line (FSL) rats display alterations in these systems relatively to their control strain Flinders Resistant Line (FRL). However, changes on transcript level related to serotonergic and glutamatergic signaling have only been sparsely studied in this model. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has fast-onset antidepressant properties, and recent data implicate serotonergic neurotransmission in ketamine's antidepressant-like activities in rodents. Here, we investigated the transcript levels of 40 genes involved in serotonergic and glutamatergic neurotransmission in FSL and FRL rats in response to a single dose of ketamine (15 mg/kg; 90 min prior to euthanization). Using real-time quantitative polymerase chain reaction, we studied the effect of ketamine in the hippocampus, whereas strain differences were investigated in both hippocampus and frontal cortex. The expression of genes involved in serotonergic and glutamatergic neurotransmission were unaffected by a single dose of ketamine in the hippocampus. Relative to FRL rats, FSL rats displayed enhanced hippocampal transcript levels of 5-ht , and P11, whereas the expression was reduced for 5-ht , Nr2a, and Mglur2. In the frontal cortex, we found higher transcript levels of 5-ht and Mglur2, whereas the expression of 5-ht was reduced in FSL rats. Thus, ketamine is not associated with hippocampal alterations in serotonergic or glutamatergic genes at 90 min after an antidepressant dose. Furthermore, FSL rats display serotonergic and glutamatergic abnormalities on gene expression level that partly may resemble findings in MDD patients.

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“…Nevertheless, it has been reported that MIR treatment induces a decrease in density of 5-HT 2A R, 43 a receptor which has been suggested to be involved in the sedative effects of MIR. Additionally, various reports indicate that the high binding affinity and agonist profile of MIR for H1 receptors seems to play an important role in its sedative effects.…”

Section: Experiments 2: Effect Of Chronic Mir Dosing On Sedationmentioning

confidence: 99%

Chronic dosing with mirtazapine does not produce sedation in rats

Salazar-Juárez

Barbosa-Méndez

Merino-Reyes

et al. 2017

Rev. Bras. Psiquiatr.

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Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

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Evaluation of 5-HT2A and mGlu2/3 receptors in postmortem prefrontal cortex of subjects with major depressive disorder: Effect of antidepressant treatment

Cited by 65 publications

References 55 publications

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future

Gene expression related to serotonergic and glutamatergic neurotransmission is altered in the flinders sensitive line rat model of depression: Effect of ketamine

Chronic dosing with mirtazapine does not produce sedation in rats

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