Blunted temperature and cortisol responses to ipsapirone in major depression: lack of enhancement by electroconvulsive therapy

Shapira, Baruch; Newman, Morris; Gelfin, Yevgenia; Lerer, Bernard

doi:10.1016/s0306-4530(99)00067-0

Cited by 45 publications

(41 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results provide a mechanistic rationale for future attempts to target the dysfunction of 5-HT1A autoreceptor as a means of treating HD-associated depression. Consistent with observations in depressed patients (Meltzer and Maes, 1995;Stockmeier et al, 1998;Shapira et al, 2000;Riedel et al, 2002;Miller et al, 2009;Sullivan et al, 2009) and several mouse models of depression (McKittrick et al, 1995;Overstreet, 2002;El Yacoubi et al, 2003;Mato et al, 2007;Richardson-Jones et al, 2010), we also found that 5-HT1A heteroreceptor function was reduced in female HD animals. Indeed, […”

Section: Discussionsupporting

confidence: 91%

“…Using a similar experimental approach in a mouse model of depression, Hensler et al (2010) suggested that hippocampal 5-HT1ARs were regulated by corticosterone. Supporting the evidence of a possible desensitization of hippocampal 5-HT1AR in patients with major depression (Shapira et al, 2000;Riedel et al, 2002; but also see Navines et al, 2007;Miller et al, 2009), we found the corticosterone response to the 5-HT 1AR agonist 8-OH-DPAT was attenuated in female HD mice.…”

Section: Discussionsupporting

confidence: 85%

See 1 more Smart Citation

Treatment of depressive‐like behaviour in Huntington's disease mice by chronic sertraline and exercise

Renoir

Pang

Zajac

et al. 2012

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEDepression is the most common psychiatric disorder in Huntington's disease (HD) patients. Women are more prone to develop depression and such susceptibility might be related to 5-hydroxytryptaminergic (serotonergic) dysregulation. EXPERIMENTAL APPROACHWe performed tests of depression-related behaviours on female R6/1 HD mice that had been chronically treated with sertraline or provided with running-wheels. Functional assessments of 5-HT1A and 5-HT2A receptors were performed by measuring behavioural and physiological responses following administration of specific agonists, in combination with analysis of hippocampal gene expression. Finally we assessed the effect of exercise on hippocampal cell proliferation. KEY RESULTSFemale HD mice recorded increased immobility time in the forced-swimming test, reduced saccharin preference and a hyperthermic response to stress compared with wild-type animals. These alterations were improved by chronic sertraline treatment. Wheel-running also resulted in similar improvements with the exception of saccharin preference but failed to correct the hippocampal cell proliferation deficits displayed by HD mice. The benefits of sertraline treatment and exercise involved altered 5-HT1A autoreceptor function, as demonstrated by modulation of the exaggerated 8-OH-DPAT-induced hypothermia exhibited by female HD mice. On the other hand, sertraline treatment was unable to restore the reduced 5-HT1A and 5-HT2 heteroceptor function observed in HD animals. CONCLUSIONS AND IMPLICATIONSWe report for the first time a crucial role for 5-HT1A autoreceptor function in mediating the sex-specific depressive-like phenotype of female R6/1 HD mice. Our data further support a differential effect of chronic sertraline treatment and exercise on hippocampal cell proliferation despite common behavioural benefits.Abbreviations 5-CT, 5-carboxamidotryptamine; 5-HTT, 5-HT transporter; AUC, area under curve; BDNF, brain-derived neurotrophic factor; BrdU, 5-bromo-2′-deoxyuridine; FST, forced-swimming test; GR, glucocorticoid receptor; HD, Huntington's disease; HPA, hypothalamic-pituitary-adrenal; RW, running-wheel; SH, standard-housed; SSRIs, selective 5-HT re-uptake inhibitors; TST, tail-suspension test; WT, wild-type BJP British Journal of Pharmacology DOI:10.1111DOI:10. /j.1476DOI:10. -5381.2011 British Journal of Pharmacology (2012) IntroductionHuntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG repeats in exon 1 of the huntingtin gene (The Huntington's Disease Collaborative Research Group, 1993). Clinical diagnosis of HD is determined on the basis of motor symptoms; however, the pre-motor stages of the disease are commonly associated with psychiatric manifestations including depression (Paulsen et al., 2005;Duff et al., 2007;Julien et al., 2007;Marshall et al., 2007). Depression is one of the most prevalent causes of disability worldwide and is diagnosed in women more frequently than in men (Fava and Kendler, 2000;Kornstein e...

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 85%

Treatment of depressive‐like behaviour in Huntington's disease mice by chronic sertraline and exercise

Renoir

Pang

Zajac

et al. 2012

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…The sensitivity and binding potential of 5-HT 1A receptors, including those located in the DRN, were shown to be attenuated in depressed patients (Cowen et al, 1994;Drevets et al, 1999;Lesch 1991;Sargent et al, 2000;Shapira et al, 2000). The present data suggest that these 5-HT 1A receptor deficits may be secondary to the cortisol abnormalities frequently seen during episodes of depression (Deuschle et al, 1997;Wong et al, 2000).…”

Section: Discussionsupporting

confidence: 48%

“…The 5-HT 1A receptor is expressed both as a postsynaptic receptor in the forebrain and as an autoreceptor on 5-HT neurones in the raphe nuclei (Pazos and Palacios, 1985;Verge et al, 1985Verge et al, , 1986. Depressed patients exhibit an attenuation of 5-HT 1A receptor mediated neuroendocrine and hypothermic responses, reflecting dysfunction of postsynaptic 5-HT 1A receptors and 5-HT 1A autoreceptors, respectively (Lesch, 1991;Cowen et al, 1994;Shapira et al, 2000). Furthermore, a decrease in the 5-HT 1A binding potential, as determined by positron emission tomography, has been demonstrated in multiple forebrain areas of depressed patients (Drevets et al, 1999;Sargent et al, 2000) as well as in the raphe (Drevets et al, 1999(Drevets et al, , 2000Sargent et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Flattening the Corticosterone Rhythm Attenuates 5-HT1A Autoreceptor Function in the Rat: Relevance for Depression

Leitch

Ingram

Young

et al. 2003

Neuropsychopharmacol

View full text Add to dashboard Cite

Depression is associated with glucocorticoid abnormalities, in particular a flattening of the diurnal cortisol rhythm. Recent data suggest that an important factor in the aetiology of depression may be a deficit in the function and expression of 5-HT 1A receptors, which has been reported in depressed patients. The present study assessed the possibility that this cortisol abnormality is causal in the 5-HT 1A receptor deficits. First, a rat model of flattened glucocorticoid rhythm was developed. Controlled release corticosterone pellets implanted for 14 days flattened the corticosterone rhythm and maintained levels constant midway between the nadir and zenith levels observed in sham-operated rats. Secondly, using microdialysis to assess 5-HT release in the hippocampus, the inhibitory response to 8-OHDPAT was measured to determine the sensitivity of somatodendritic 5-HT 1A autoreceptors. Corticosterone treatment was found to induce a significant attenuation in the response to 8-OHDPAT, indicating functional desensitization of somatodendritic 5-HT 1A autoreceptors. There was no effect of corticosterone treatment on basal extracellular 5-HT levels. The data suggest that the glucocorticoid abnormalities associated with depression may impact on the functioning of 5-HT 1A receptors in the brain. These findings suggest that resolution of cortisol abnormalities may be a valuable target for pharmacotherapy in the treatment of depression.

show abstract

“…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).…”

mentioning

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

View full text Add to dashboard Cite

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...

show abstract

Blunted temperature and cortisol responses to ipsapirone in major depression: lack of enhancement by electroconvulsive therapy

Cited by 45 publications

References 60 publications

Treatment of depressive‐like behaviour in Huntington's disease mice by chronic sertraline and exercise

Treatment of depressive‐like behaviour in Huntington's disease mice by chronic sertraline and exercise

Flattening the Corticosterone Rhythm Attenuates 5-HT1A Autoreceptor Function in the Rat: Relevance for Depression

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

Contact Info

Product

Resources

About