5-HT1A receptor function in depression: effect of chronic amitriptyline treatment

Lesch, Klaus‐Peter; Disselkamp-Tietze, J.; Schmidtke, Armin

doi:10.1007/bf01257081

Cited by 72 publications

(32 citation statements)

References 10 publications

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“…The second possibility is that alterations in 5-HT 1A receptor function are functionally relevant to mood when they occur in the clinical (and neurobiological) context of depression but not in normal subjects. Blunted hypothermic (Lesch et al 1990c, Cowen et al 1994, ACTH and cortisol (Lesch et al 1990d;Meltzer and Maes 1994) responsiveness to 5-HT 1A receptor agonists, including ipsapirone, have been reported in depressed patients and a reduced hypothermic response to ipsapirone was observed following chronic antidepressant (amitriptyline) administration (Lesch et al 1990e). Further studies on the effect of SSRIs on 5-HT 1A receptor-mediated hypothermic and neuroendocrine responses in depressed patients are needed in order to address this question.…”

Section: Discussionmentioning

confidence: 99%

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Lerer¹,

Gelfin²,

Gorfine

et al. 1999

Neuropsychopharmacology

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Serotonergic receptors of the 5-HT 1A subtype have been suggested to play a pivotal role in the mechanism of action of antidepressant drugs, including specific serotonin reuptake inhibitors (SSRIs). We examined the effect of clinical doses of the SSRI, fluoxetine, on 5-HTThere is considerable interest in the role of serotonergic (5-HT) receptors of the 5-HT 1A subtype in the therapeutic action of antidepressant drugs. 5-HT 1A receptors are located presynaptically on serotonergic cell bodies in the raphe nuclei where they serve as autoreceptors which inhibit cell firing and reduce 5-HT release by a negative feedback mechanism, and post-synaptically in the hippocampus, cortex and other brain areas, including the hypothalamus. Based on electrophysiological studies in rats, De Montigny and colleagues Mongeau et al. 1997) proposed that each major class of antidepressants increases 5-HT neurotransmission by a distinct mechanism involving either From the Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah-Hebrew University Medical Center (BL, YG, MEN) and the Laboratory of Applied Statistics, Hebrew University (MG), Jerusalem, Israel; the Endocrine Laboratory, Department of Medicine (BA) and Department of Psychiatry (KPL), University of Wuerzburg, Wuerzburg, Germany.Address correspondence to: Prof. Bernard Lerer, Biological Psychiatry Laboratory, Dept. of Psychiatry, Hadassah-Hebrew University Medical Center, Ein Karem, Jerusalem 91120, Israel.Received May 15, 1998; accepted August 25, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 6 Ipsapirone Challenge in Normal Subjects on Fluoxetine 629pre-or post-synaptic 5-HT 1A receptors. The selective serotonin re-uptake inhibitors (SSRIs), which raise 5-HT synaptic levels when given acutely, were proposed to increase 5-HT transmission on repeated administration by inducing desensitization of somatodendritic 5-HT 1A autoreceptors in the raphe nuclei and nerve terminal 5-HT 1B autoreceptors, which also mediate feedback inhibition of 5-HT release. These effects would lead to a slow increase in 5-HT levels which corresponds to the delayed clinical effect of the drugs. Evidence for subsensitivity of somatodendritic 5-HT 1A autoreceptors after chronic administration of SSRIs has been provided by microdialysis experiments in which 5-HT levels are measured in vivo in response to a challenge dose of the 5-HT 1A receptor agonist, 8-hydroxy-2 (di-n-propylamino) tetralin (8-OH-DPAT) (Rutter et al. 1994, Kreiss andLucki 1995;Invernizzi et al. 1994). However, other studies using SSRIs (Hjorth and Auerbach 1994; Bosker et al. 1995a,b;Invernizzi et al. 1995Invernizzi et al. , 1996 or clomipramine (Gur et al. 1999) failed to show any change in 5-HT 1A autoreceptor subsensitivity by this method. An increase in basal 5-HT levels after chronic SSRI administration, taken to be due to pre-synaptic 5-HT 1A and 5-HT 1B receptor desensitization, has been observed in cortex (Bel and Artigas 1993), hippocampus (Auerbach and Hjorth 1995) diencephalon (Rutter et al. 1994) an...

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Section: Discussionmentioning

confidence: 99%

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

Lerer¹,

Gelfin²,

Gorfine

et al. 1999

Neuropsychopharmacology

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“…The 5-HT 1A receptor system in particular has been implicated in the pathophysiology of depression, and antidepressant drug mechanisms. Depressed subjects showed blunted response to 5-HT 1A agonists in vivo and decreased 5-HT 1A receptor binding postmortem (29)(30)(31). Drevets et al (11,12) and Sargent et al (45) found reduced 5-HT 1A receptor binding potential in subjects with familial depression relative to controls in regions including raphe and mesiotemporal cortex.…”

Section: Introductionmentioning

confidence: 98%

5-HT1A Receptor Binding in Temporal Lobe Epilepsy Patients With and Without Major Depression

Hasler

Bonwetsch

Giovacchini

et al. 2007

Biological Psychiatry

129

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Background-Major depressive disorder (MDD) is the most common comorbid psychiatric condition associated with temporal lobe epilepsy (TLE). Preclinical and clinical studies suggest that 5-HT 1A receptors play a role in the pathophysiology of both TLE and MDD. There is preliminary evidence for an association between decreased 5-HT 1A receptor binding in limbic brain areas and affective symptoms in TLE patients. The objective of this study was to compare 5-HT 1A receptor binding between TLE patients with and without MDD. For the first time, 5-HT 1A receptor binding was measured in a sample large enough to permit sensitive comparisons between TLE patients with and without comorbid MDD diagnosed by clinical and structured psychiatric interviews.

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“…Two recent neuroendocrine challenge studies using the 5-HT la agonist ipsapirone also lend support for differences in 5-HTla receptor function in MOD. The frrst study found that the hypo thermic response to ipsapirone was attenuated after amitriptyline treatment (Lesch et al 1990). The second study by the same group found a blunted ipsapirone induced adrenocorticotrophic hormone (ACTH) re sponse in patients with MOD compared to controls (Lesch et al 1991).…”

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confidence: 99%

A Preliminary Neuroendocrine Study with Buspirone in Major Depression

Moeller

Steinberg

Fulton

et al. 1994

Neuropsychopharmacol

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We administered the serotonin-1a agonist buspirone (0.4 mglkg orally) as a neuroendocrine challenge agent to a group of male patients with DSM-III -R major depressive disorder (MOD) (n = 13) and a group of male healthy controls (n = 10). The primary hypothesis of the study was that the prolactin response to buspirone would be blunted in the depressed patients. The prolactin response was significantly lower in depressed patients than in controls. There was no significant relationship between KEY WORDS: Depressive disorder; Serotonin; Buspirone; Prolactin 655 Avenue of the Americas, New York, NY 10010 placebo corrected-peak prolactin level and severity of depression or suicidality. There was a nonsignificant trend for the melancholic (n = 5) depressed patients to have a lower placebo corrected-peak prolactin level than nonmelancholic depressed patients (n = B).Our findings support a role for the serotonin-1a receptor in the etiology of MOD, specifically at the postsynaptic site. and 5-HT -releasing agents (Siever et al. 1984; Coccaro et al. 1989;Mitchell and Smythe 1990;Lichtenberg et al. 1992;Shapira et al. 1992aShapira et al. , 1992b.There has been a relatively consistent ii.nding of de creased prolactin response to various serotonergic agents in subjects with major depressive disorder (MOD) using nonspecific 5-HT challenge agents; thus, recent research has focused on the role of specific subtypes

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5-HT1A receptor function in depression: effect of chronic amitriptyline treatment

Cited by 72 publications

References 10 publications

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

5-HT1A Receptor Function in Normal Subjects on Clinical Doses of Fluoxetine Blunted Temperature and Hormone Responses to Ipsapirone Challenge

5-HT1A Receptor Binding in Temporal Lobe Epilepsy Patients With and Without Major Depression

A Preliminary Neuroendocrine Study with Buspirone in Major Depression

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