Effects of triiodothyronine and fluoxetine on 5-HT1A and 5-HT1B autoreceptor activity in rat brain: regional differences

Lifschytz, Tzuri; Gur, Eitan; Lerer, Bernard; Newman, Morris

doi:10.1016/j.jneumeth.2004.03.028

Cited by 28 publications

(18 citation statements)

References 37 publications

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“…Like SSRIs, T 3 may increase serotoninergic neurotransmission in rats by desensitizing serotonin 1A autoreceptors in the raphe nucleus and serotonin 1B autoreceptors in the frontal cortex and hypothalamus, leading to increased synaptic concentrations of serotonin. [22][23][24][25] In an algorithmbased study, Agid and Lerer 26 found T 3 (25-50 µg for 3 weeks) to be effective in 10 of 25 patients nonresponsive to SSRIs. Similar response rates were observed in 2 other open-label studies.…”

mentioning

confidence: 99%

Combined Treatment With Sertraline and Liothyronine in Major Depression

Cooper‐Kazaz¹,

Apter²,

Cohen³

et al. 2007

Arch Gen Psychiatry

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mentioning

confidence: 99%

Combined Treatment With Sertraline and Liothyronine in Major Depression

Cooper‐Kazaz¹,

Apter²,

Cohen³

et al. 2007

Arch Gen Psychiatry

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“…Furthermore, we found (Gur et al, 2002;Lifschytz et al, 2004), in the context of in vivo microdialysis experiments, that the effect of T3 on 5HT 1A/1B receptor desensitization is maximal only after at least 2 weeks of T3 administration. We chose to comprehensively evaluate the antidepressant-like attributes of T3 as a sole pharmacotherapeutic agent because this has not been done previously and is important in understanding the antidepressant-like mechanism(s) of this agent.…”

Section: Discussionmentioning

confidence: 73%

“…A putative mechanism for the antidepressant effects of T3 is down-regulation of inhibitory, presynaptic 5-HT 1A and 5-HT 1B receptors (Gur et al, 1999(Gur et al, , 2002Lifschytz et al, 2004). In mice, 8-OH-DPAT-induced hypothermia represents a model for the level of activity of somatodendritic, inhibitory, presynaptic raphe 5HT 1A receptors (Bill et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…In this context, we have shown ) that chronically administered T3 induces a reduction in 5-HT 1A (presynaptic in raphe nucleus and postsynaptic in various forebrain areas) and 5-HT 1B receptor expression (presynaptic in raphe and pre-and postsynaptic in forebrain areas). Effects of T3 on the serotonergic system have been studied previously in relation to the antidepressant effects of the hormone (Newman et al, 2000;Bauer et al, 2002) with evidence from functional and behavioral studies (Heal and Smith, 1988) and in vivo microdialysis experiments (Gur et al, 1999(Gur et al, , 2002Lifschytz et al, 2004) for a reduction in the activity of inhibitory, presynaptic 5-HT 1A and 5-HT 1B receptors.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Triiodothyronine on Antidepressant Screening Tests in Mice and on Presynaptic 5-HT1A Receptors: Mediation by Thyroid Hormone α Receptors

Lifschytz

Zozulinsky²,

Eitan³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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Although triiodothyronine (T3) is widely used clinically, preclinical support for its antidepressant-like effects is limited, and the mechanisms are unknown. We evaluated 1) the antidepressantlike effects of T3 in the novelty suppressed feeding test (NSFT), tail suspension test (TST), and forced swim test (FST), 2) the role of presynaptic 5-HT 1A receptors in the antidepressant-like mechanism of T3 by the hypothermic response to the 5-HT 1A receptor agonist, 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), 3) the thyroid hormone receptor type mediating the antidepressant-like effects by concurrent administration of the specific thyroid hormone ␣ receptor (TR␣) antagonist, dronedarone, and 4) the presence of these effects in both genders. Male and female BALB/c mice were administered 1) T3 (20, 50, 200, or 500 g/kg per day) or vehicle or 2) T3 (50 g/kg per day), dronedarone (100 M/day), or the combination intraperitoneally for 21 days and then underwent a behavioral test battery. The NSFT showed a shortened latency to feed in males at the two lower T3 doses. The TST and FST showed decreased immobility in male mice at T3 doses Ͼ20 g/kg per day and in females at all T3 doses. Concurrent dronedarone prevented T3 effects in males on the NSFT and in the TST and FST in both genders. Attenuation of 8-OH-DPAT-induced hypothermia was observed in males only and may be reduced by concurrent dronedarone. These findings support an antidepressant-like effect of T3. Attenuation of 8-OH-DPAT-induced hypothermia in males only suggests the need to evaluate a possible gender disparity in the role of presynaptic 5-HT 1A receptors in T3 antidepressant mechanisms. Blockade by dronedarone of the antidepressant-like effects of T3 suggests that these effects are TR␣ receptor-mediated.

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“…From a disease mechanism point of view, the slow onset of efficacy observed across the spectrum of monoamine re-uptake inhibitors is incongruent with the primary mechanism of action of the drug. Many preclinical animal studies have demonstrated that blockade of re-uptake of neurotransmitters occurs within hours following drug administration [21][22][23]. However, most people with depression exhibit a delay in the therapeutic response that can be ≥ 4 -6 weeks.…”

Section: Treatment Strategies For Depression 21 the Tricyclics And Mmentioning

confidence: 99%

The corticotropin-releasing factor receptor: a novel target for the treatment of depression and anxiety-related disorders

Grigoriadis

2005

Expert Opinion on Therapeutic Targets

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The treatment of mood disorders has been the subject of intense study for more than half a century and has resulted in the discovery and availability of a number of compounds that have seen tremendous success in the management of major depression and anxiety-related disorders. In spite of this success, these drugs have not provided a complete therapeutic solution for all patients and this has revitalised the need for a greater understanding of the underlying molecular mechanisms and targets involved in these disorders. Elucidation of these novel targets will enable the development of a better class of compounds which could benefit a greater majority of the patient population and be devoid of the current side effect liabilities. Towards that end, this review examines, in detail, the prospect of one such target, the corticotropin-releasing factor system, as having an enhanced therapeutic profile with the potential of a broader range of efficacy with reduced side effect liabilities.

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Effects of triiodothyronine and fluoxetine on 5-HT1A and 5-HT1B autoreceptor activity in rat brain: regional differences

Cited by 28 publications

References 37 publications

Combined Treatment With Sertraline and Liothyronine in Major Depression

Combined Treatment With Sertraline and Liothyronine in Major Depression

Effect of Triiodothyronine on Antidepressant Screening Tests in Mice and on Presynaptic 5-HT1A Receptors: Mediation by Thyroid Hormone α Receptors

The corticotropin-releasing factor receptor: a novel target for the treatment of depression and anxiety-related disorders

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