5-Hydroxytryptamine1A Receptor Responsivity in Obsessive-Compulsive Disorder

Lesch, K.P.; Hoh, A.; Disselkamp-Tietze, J.; Wiesmann, Martin; Osterheider, Michael; Schulte, Heinrich M.

doi:10.1001/archpsyc.1991.01810300052007

Cited by 66 publications

(18 citation statements)

References 66 publications

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“…However, others pointed out that the severity of depression must be taken into account, since a positive correlation between severity of disease and hypothermic responses after IPS could be demonstrated [43]. In patients with panic disorder, neuroendocrine and thermoregulatory responses to IPS were attenuated probably reflecting a subsensitivity of pre-and postsynaptic 5-HT 1a receptors, but obsessive-compulsive patients did not differ from controls in neuroendocrine or thermoregulatory responses after treatment with IPS [44].…”

Section: Introductionmentioning

confidence: 99%

Endocrine Responses after <i>d</i>-Fenfluramineand Ipsapirone Challenge: Further Support for Cloninger’s Tridimensional Model of Personality

et al. 2000

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The tridemensional model of personality introduced by Cloninger relates aspects of novelty seeking to the dopaminergic, harm avoidance (HA) to the serotonergic, and reward dependence to the noradrenergic neurotransmitter system. Using a neuroendocrine challenge paradigm, this study investigates whether subjects characterized by blunted cortisol (CORT) responses after ipsapirone (IPS) relate to different subfactors of HA from those characterized by blunted prolactin (PRL) responses after treatment with d-fenfluramine (D-FEN). Moreover, subjects blunted in both responses should differ in scale values of subfactors of HA from those with only one or no blunted reactions. In the first part of the experiment, 16 healthy male volunteers were treated with 15 mg D-FEN. The second part of the study (about 1 year later) consists of a challenge with the partial 5-hydroxytryptamine-1a (5-HT_1a) agonist IPS (10 mg) in the same subjects. The results indicate that blunted PRL responses are accompanied by high values in HA, while the main effect of IPS responsivity did not relate significantly to this dimension. With respect to the subscales of HA, subjects blunted in both responses (PRL–/C–) exhibit significantly higher levels in fatigability and asthenia when compared to all other groups (PRL–/C+, PRL+/C–,PRL+/C+). The data demonstrate that combined challenge tests may shed more light on the biological basis of personality and that HA and most clearly fatigability and asthenia relate to the 5-HT system.

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Section: Introductionmentioning

confidence: 99%

Endocrine Responses after <i>d</i>-Fenfluramineand Ipsapirone Challenge: Further Support for Cloninger’s Tridimensional Model of Personality

et al. 2000

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“…Other compounds that have been used in challenge studies in OCD are sodium lactate, ipsapirone, clonidine and fenfluramine Bastani et al 1990;Hollander et al 1991;Lesch et al 1991;McBride et al 1992). None of these probes showed the ability to exacerbate obsessive-compulsive symptoms, although an increase in anxiety was frequently reported.…”

Section: Introductionmentioning

confidence: 99%

Pentagastrin has panic-inducing properties in obsessive compulsive disorder

deLeeuw¹,

DenBoer²,

Slaap³

et al. 1996

Psychopharmacology

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The effects of the CCKB-receptor agonist pentagastrin, a synthetic analogue of the cholecystokinin tetrapeptide (CCK-4), were studied in seven patients suffering from obsessive compulsive disorder (OCD) and seven healthy controls. All subjects were challenged with an IV dose of 0.6 micrograms/kg pentagastrin or placebo under double blind placebo controlled conditions, on two separate occasions, with a minimum interval of 1 week. Six (86%) out of seven OCD patients experienced a panic-like reaction after pentagastrin administration, against only two (29%) in the control group. These differences failed to reach statistical significance, probably due to the small sample size. No increases were observed in obsessions or compulsive behaviors as assessed with the Yale-Brown Obsessive Compulsive Challenge Scale, neither in the pentagastrin, nor in the placebo condition. These findings suggest that pentagastrin has panic-inducing properties in OCD patients, without affecting the core symptoms. The panic-inducing properties of pentagastrin are not specific for panic disorder patients, which might be indicative of a common neurobiological dysfunction in panic disorder and OCD at the level of CCK-B receptors.

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“…These data indicate that 5-HT1A receptor stimulation in the PVN mediates the characteristic neuroendocrine response to serotonin agonist challenge. Moreover, they provide the first evidence that aspects of the behavioral serotonin syndrome are mediated by forebrain hypothalamic receptors.Measurements of hormone release and thermoregulatory responses to acute challenge with serotonergic releasing agents or clinically approved partial 5-HT1A receptor agonists have been used to assess the sensitivity of serotonergic function in patients suffering from various psychological disorders such as depression, obsessive compulsive disorder, or post-traumatic stress (Lesch et al, 1990a(Lesch et al, , 1991Flory et al, 1998;Rinne et al, 2000;Shapira et al, 2000). Administration of serotonin-releasing agents, as well as 5-HT1A receptor agonists, produces a distinct profile of stress hormone release characterized, in part, by increased plasma levels of adrenocorticotropin hormone (ACTH), prolactin, and cortisol in human subjects Sherman, 1984, 1985; Lesch et al, 1990a,b).…”

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confidence: 99%

5-Hydroxytryptamine 1A Receptors in the Paraventricular Nucleus of the Hypothalamus Mediate Oxytocin and Adrenocorticotropin Hormone Release and Some Behavioral Components of the Serotonin Syndrome

Osei‐Owusu

James²,

Crane³

et al. 2005

J Pharmacol Exp Ther

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Neuroendocrine responses to administration of serotonin releasing agents or 5-hydroxytryptamine (5-HT) 1A receptor agonists have been used as an index of serotonin receptor function in patients with depression and other mood disorders. However, the receptor population that mediates these responses has not been clearly identified. We tested the hypothesis that 5-HT1A receptors in the paraventricular nucleus of the hypothalamus (PVN) mediate the release of adrenocorticotropin hormone (ACTH) and oxytocin after administration of a selective 5-HT1A agonist in conscious rats. Low-dose infusion (1 nmol/ 100 nl/side) of the selective 5-HT1A antagonist, WAY100635 (WAY; [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-(2-pyridinyl)cyclohexanecarboxamidetrihydrochloride), into the PVN blocked the rise in ACTH and oxytocin stimulated by low-dose (30 nmol/kg) i.v. administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 274 Ϯ 53 versus 70 Ϯ 20 pg/ml, P Ͻ 0.01 for ACTH and 10.7 Ϯ 3.4 versus 4.6 Ϯ 0.7 pg/ml, P Ͻ 0.05 for oxytocin after saline or WAY pretreatment, respectively). WAY did not influence the bradycardic effect of 8-OH-DPAT (Ϫ56 Ϯ 7 versus Ϫ54 Ϯ 6 beats per minute after saline or WAY). 8-OH-DPAT treatment also elicited locomotor activation followed by hind limb abduction and flat body posture. Surprisingly, WAY attenuated some aspects of locomotor activation and reduced the duration of hind limb abduction elicited by the agonist (5.1 Ϯ 0.9 versus 0.3 Ϯ 0.3 min for saline-or WAY-treated rats). These data indicate that 5-HT1A receptor stimulation in the PVN mediates the characteristic neuroendocrine response to serotonin agonist challenge. Moreover, they provide the first evidence that aspects of the behavioral serotonin syndrome are mediated by forebrain hypothalamic receptors.Measurements of hormone release and thermoregulatory responses to acute challenge with serotonergic releasing agents or clinically approved partial 5-HT1A receptor agonists have been used to assess the sensitivity of serotonergic function in patients suffering from various psychological disorders such as depression, obsessive compulsive disorder, or post-traumatic stress (Lesch et al., 1990a(Lesch et al., , 1991Flory et al., 1998;Rinne et al., 2000;Shapira et al., 2000). Administration of serotonin-releasing agents, as well as 5-HT1A receptor agonists, produces a distinct profile of stress hormone release characterized, in part, by increased plasma levels of adrenocorticotropin hormone (ACTH), prolactin, and cortisol in human subjects Sherman, 1984, 1985; Lesch et al., 1990a,b). Depressed patients demonstrate a blunted release of ACTH and cortisol in response to acute administration of partial 5-HT1A receptor agonists (Lesch et al., 1990a;Shapira et al., 2000). Positron emission tomography studies demonstrate reduced 5-HT1A receptor binding in several brain regions in both depressed patients as well as those diagnosed with panic disorder (Sargent et al., 2000;Neumeister et al., 2004). The...

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5-Hydroxytryptamine1A Receptor Responsivity in Obsessive-Compulsive Disorder

Cited by 66 publications

References 66 publications

Endocrine Responses after <i>d</i>-Fenfluramineand Ipsapirone Challenge: Further Support for Cloninger’s Tridimensional Model of Personality

Endocrine Responses after <i>d</i>-Fenfluramineand Ipsapirone Challenge: Further Support for Cloninger’s Tridimensional Model of Personality

Pentagastrin has panic-inducing properties in obsessive compulsive disorder

5-Hydroxytryptamine 1A Receptors in the Paraventricular Nucleus of the Hypothalamus Mediate Oxytocin and Adrenocorticotropin Hormone Release and Some Behavioral Components of the Serotonin Syndrome

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