Effects of Lithium on the Hypothalamo-Pituitary-Adrenal Axis.

Sugawara, Masanori; Hashimoto, Kozo; Hattori, Teruhiko; Takao, Toshihiro; Suemaru, Shuso; Ota, Zensuke

doi:10.1507/endocrj1954.35.655

Cited by 30 publications

(24 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In rats and in cultured pituitary cells, ACTH and corticosterone were significantly increased after lithium administration, possibly by directly acting on the corticotrophs (Zatz and Reisine 1985;Reisine and Zatz 1987;Sugawara et al 1988). However, in our study, ACTH serum levels before CRH stimulation were not significantly different between baseline and re-assessment.…”

Section: T Bschor Et Alcontrasting

confidence: 85%

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Bschor

Adli

Baethge

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

Lithium augmentation is a well established strategy for treatment-resistant depression. The exact mode of its action is unknown, but an enhancement of serotonergic transmission is hypothesized. The authors investigated changes in the hypothalamic-pituitary-adrenocortical (HPA) system during lithium augmentation and their correlation to clinical response by means of the combined dexamethasone/CRH test (DEX/CRH test). Thirty patients with unipolar major depressive episodes (DSM IV) who had not responded to an adequate trial with an antidepressantwere assessed on the day before lithium augmentation (baseline) with the DEX/CRH test (pretreatment with 1.5 mg dexamethasone p.o. at 11 P . M . and CRH stimulation at 3 P . M . on the next day). Twenty-four patients were reassessed after response was determined or, in cases of nonresponse, four weeks after initiation of lithium augmentation. Response to lithium augmentation was measured by weekly ratings on the Hamilton DepressionRating Scale Regardless of the initial choice of antidepressant, about 30 to 40% of patients with major depressive disorder will not respond sufficiently (Thase and Rush 1995 Among the various treatment options that have been proposed for non-responding depressed patients, lithium augmentation has been recommended as a first-line strategy . The efficacy of lithium augmentation has been well documented in placebo-controlled acute (Joffe et al. 1993;Katona et al. 1995;Baumann et al. 1996) and continuation treatment trials (Bauer et al. 2000;Bschor et al. 2002) using different classes of antidepressants. A recent meta-analysis confirmed the evidence that lithium augmentation is superior to placebo augmentation for the treatment of unipolar major depression, with a median response rate of 50% across double-blind studies (Bauer and Döpfmer 1999). Severity of depression was recently identified as a clinical predictor of response to lithium augmentation (Bschor et al. 2001). Better knowledge of the neurobiological mechanisms of lithium augmentation would help to identify patients who will respond favorably to this treatment intervention. However, to date, the mode of action of lithium augmentation is unknown. Shortly after the initial report on its efficacy (de Montigny et al. 1981), it was postulated by de Montigny et al. (1983) that a pharmacodynamic action mediated via the serotonergic systems might account for the synergistic effect of lithium when added to a tricyclic antidepressant.Another system potentially involved in its mechanism of action is the hypothalamic-pituitary-adrenocortical (HPA) system, putatively the best studied biological system in affective disorders (Dinan 1997). The most sensitive challenge test of the HPA system is the combined dexamethasone/CRH test (DEX/CRH test) (Heuser 1998). A dysfunction in the regulation of the HPA system, especially an overstimulation of ACTH and cortisol in the DEX/CRH test, was repeatedly shown in depressed patients (for a review see Steckler et al. 1999;Holsboer 2000). In treatment studies with ...

show abstract

Section: T Bschor Et Alcontrasting

confidence: 85%

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Bschor

Adli

Baethge

et al. 2002

Neuropsychopharmacology

View full text Add to dashboard Cite

show abstract

“…A similar process involving a hormonal or neurotransmitter system may be important for the inclusion of the amygdala in odor-malaise conditioning. LiCl does activate the hypothalamic-pituitary-adrenal axis (Sugawara et al 1988;Spencer et al 2005), which has been implicated in both adult and infant malaise conditioning Smotherman et al 1976;Smotherman 1985;Kent et al 2002;Tenk et al 2006). However, corticosterone does not appear necessary for odor/taste aversion Smotherman 1985), although this requires further exploration.…”

Section: Learning and Memory 803mentioning

confidence: 99%

Development switch in neural circuitry underlying odor-malaise learning

Shionoya¹,

Moriceau²,

Lunday³

et al. 2006

Learn. Mem.

View full text Add to dashboard Cite

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.Animals rapidly learn to avoid tastes, smells, and textures of foods associated with malaise, and this learning process produces conditioned taste and odor aversions (Garcia et al. 1966(Garcia et al. , 1974 Best 1992, 1993). This learning has been demonstrated early in development, including both the embryonic day (ED) 18 rat and mouse fetuses, with retention time lasting weeks Haroutunian and Campbell 1979;Smotherman 1982;Stickrod et al. 1982b;Rudy and Cheatle 1983; Robinson 1985, 1990;Alleva and Calamandrei 1986;Molina et al. 1986;Hoffmann et al. 1987Hoffmann et al. , 1990Miller et al. 1990;Hunt et al. 1991Hunt et al. , 1993Abate et al. 2001;Richardson and McNally 2003;Gruest et al. 2004a). Taste/odor aversion acquisition shows some specific differences between pups and adults. First, nursing during acquisition disturbs taste-aversion learning, although this diminishes as pups approach weanling (Martin and Alberts 1979;Gubernick and Alberts 1984;Melcer et al. 1985;Kehoe and Blass 1986). Second, in contrast to the long temporal parameters permitted between the odor/taste (conditioned stimulus, CS) and illness (unconditioned stimulus, US) in adult taste aversion, the temporal constraints between the CS and the malaise producing US for pup learning are very limited (Rudy and Cheatle 1983;Kraemer et al. 1988Kraemer et al. , 1989Hoffmann et al. 1990Hoffmann et al. , 1991.There is evidence that the neural basis of odor/taste aversion learning may change over development. In adults, the amygdala is thought to support taste-aversion learning, though there are discrepancies in the literature (Nachman and Ashe 1974;Burt and Smotherman 1980;Dunn and Everitt 1988;Yamamoto and Fujimoto 1991;Kesner et al. 1992;Yamamoto et al. 1994;Bures et al. 1998;Schafe et al. 1998;Sakai and Yamamoto 1999;Wilkins and Bernstein 2006). When the taste and smell component...

show abstract

“…1). Presumably, LH has a direct effect on the average daily level of CS, since lithium has been shown to activate the hypothalamus-pituitary-adrenal system [13,14]. After morning administration of LH, 21-h harmonics with acrophases shifted to earlier morning hours were predominant in the spectra of both parameters; the peak of 5-HT content in the brain preceded the maximum plasma concentration of the hormone (Fig.…”

Section: Resultsmentioning

confidence: 96%

Effect of lithium hydroxybutyrate on circadian rhythms of brain serotonin content and plasma corticosteroids in reserpine-treated mice

1997

View full text Add to dashboard Cite

Lithium hydroxybutyrate (10 mg/kg daily for 10 days, intramuscularly) administered in the morning prevents reserpine-induced depression of the diurnal steroidogenesis in mice and the development of desynchronosis between circadian rhythms of serotonin in the brain and plasma corticosteroids. Evening injections result in the formation of phase-discordant 24-h periodicities, the mean values of the studied parameters being unaffected. Key Words: circadian rhythms; reserpine; serotonin; corticosteroids; lithium hydroxybutyratePhase-dependent resynchronizing effect of lithium hydroxybutyrate (LH) was previously demonstrated by us in the model of reserpine depression [3]. Disturbed rhythmic organization of steroidogenesis in patients with affective psychosis [1] is probably related to dysfunction of the central serotoninergic system [10,12]. Taking into account the mechanism of the normothymic action of LH [4] and the fact that central effects of reserpine are mediated through monoamine system [2,7], the effect of LH on circadian rhythms of serotonin (5-HT) in the brain and plasma corticosteroids (CS) was studied in reserpinetreated mice. MATERIALS AND METHODSExperiments were carried out on male mice weighing 25-28 g during the winter solstice. The animals (40-50 mice per group) were kept under natural illuminaDepartment of Human and Animal Physiology, State University, Tomsk; Department of Pharmacology, Siberian Medical University, Tomsk; Department of Radionuclide Studies, Institute of Cardiology, Tomsk Research Center, Siberian Division of the Russian Academy of Medical Sciences tion 1-1.5 months prior to the experiment with free access to food (standard chow) and water. LH (10 mg/kg in a volume of 0.05 ml per 10 g body weight) was injected intramuscularly for 10 days either in the morning (8:30) or in the evening (19:30). Control animals received the same volume of water. On day 8 (15:00) the animals were injected with reserpine (0.75 mg/kg, subcutaneously). On the next day, brain 5-HT and plasma CS were measured every 6 h starting from 9:00. The mice (12 animals per point) were rapidly decapitated (in the night under red illumination), collected heparinized blood was centrifuged, and the plasma was used for glucocorticoid assay. The brain was rapidly removed, and the studied brain structures were isolated and stored in liquid nitrogen. The content of 5-HT (gg/g wet tissue) in brain samples (excluding the cerebellum, medulla oblongata, and olfactory bulb) was measured tluorimetrically using o-phthalaldehyde [5]. The concentration of adrenocortical hormones (glucocorticoids, nmol/ liter) was determined using steron-K-12SI-M radioimmunoassay kits (Russia) [6].The primary chronograms were subjected to spectral and cosinor-analysis [4] and statistically signiticantly rhythms were analyzed (p<0.05).

show abstract

Effects of Lithium on the Hypothalamo-Pituitary-Adrenal Axis.

Cited by 30 publications

References 38 publications

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Lithium Augmentation Increases the ACTH and Cortisol Response in the Combined DEX/CRH Test in Unipolar Major Depression,

Development switch in neural circuitry underlying odor-malaise learning

Effect of lithium hydroxybutyrate on circadian rhythms of brain serotonin content and plasma corticosteroids in reserpine-treated mice

Contact Info

Product

Resources

About