The stimulation of prolactin secretion by taurine: Studies on the site of action

Taurine's site of action within the central nervous system was localized by studying its effect on prolactin secretion following the microinfusion of 125 nmoles of this amino acid into discrete regions of the brain. Taurine was found to stimulate prolactin secretion only when microinfused into the arcuate nucleus of the hypothalamus. Taurine was not effective in other areas of the hypothalamus or in several extra-hypothalamic sites. Mannitol infusions (125 nmoles) into the arcuate nucleus, used as a control, were without effect on prolactin secretion. These studies extend previous observations on the prolactin-releasing action of centrally administered taurine and suggest further that the arcuate nucleus is one target site for this action.     

On the site of action of reserpine on ACTH secretion

Summary The studies were concerned with the site in the CNS of the action of reserpine on pituitary ACTH secretion. The medial basal hypothalamus (MBH) was totally or partially deafferented (interrupting the anterior, the posterior and superior or the posterior connections of the region and leaving intact all the other pathways), the fornix was transected or a lesion was placed in the medial ventral tegmentum of the mesencephalon, and following all these interventions plasma corticosterone levels were determined before reserpine treatment and four hours after drug administration (giving 3.0–3.5 mg/kg b.w. i.p.). In the intact rats reserpine caused a 3–5 fold increase in plasma corticosterone concentration. No elevation in blood corticoid levels occurred if the drug was administered to rats in which the MBH was completely deafferented. Similar results were obtained when only the anterior connections of the MBH were interrupted. In contrast, severance of the afferents coming to the MBH from both sides and from above, or from posterior, transection of the fornix, or a lesion in the medial ventral tegmentum of the mesencephalon did not block the mentioned effect of reserpine. The drug given to intact rats for nine days (0.7 mg/kg b.w. daily i.p.) induced a well-known marked increase in adrenal weight. Complete deafferentation of the MBH also interfered with this effect. — The data suggest that (1) the reserpine-induced CRF release is not directly exerted on the MBH; (2) the critical afferents essential for the pituitary ACTH response to reserpine reach the MBH from an anterior direction; (3) hippocampal and mesencephalic structures having direct contact with the MBH are not primarily responsible for the reserpine effect on ACTH.The findings were presented at the II. Congress of the International Society of Psychoneuroendocrinology held at Budapest, July 1–3, 1971.     

C-type natriuretic Peptide stimulates prolactin secretion by a hypothalamic site of action

The most recently discovered member of the family of natriuretic peptides, C-type natriuretic peptide (CNP), exerts many pharmacologic actions similar to its structural homolog A-type natriuretic peptide (ANP). Like ANP it failed to significantly alter prolactin release from dispersed, rat anterior pituitary cells incubated under static or dynamic conditions. Unlike ANP, however, which inhibits prolactin secretion in vivo by a hypothalamic action, CNP injection into the third cerebroventricle significantly stimulated prolactin secretion in ovariectomized, conscious rats. The effect was highly significant 15 min after injection and transient, lasting 30 min in animals injected with 2 nmole CNP. In a companion group of rats, significant inhibition of plasma prolactin levels was observed after central administration of similar doses of ANP. These results suggest differing hypothalamic actions of the CNP and ANP perhaps mediated by multiple natriuretic peptide receptors present in the tissue. Further, they provide additional support for unique roles exerted within the central nervous system by these structural homologs.     

Regulation of corticosteroid receptor gene expression in depression and antidepressant action.

OBJECTIVE: Major alterations of the hypothalamic-pituitary-adrenocortical (HPA) system are often seen in patients with depression, and can be reversed by successful antidepressant therapy. Persuasive evidence points to the involvement of a dysfunctional glucocorticoid receptor system in these changes. The authors developed a transgenic mouse to determine the mechanism for these changes. DESIGN: In vivo and in vitro animal experiments. ANIMALS: Transgenic mice expressing glucocorticoid receptor antisense RNA and control mice. INTERVENTIONS: In vivo: hormone assays and dexamethasone suppression tests; in vitro: cell transfection, chloramphenicol acetyl transferase assay, Northern blot analysis, binding assays of cytosolic receptor. OUTCOME MEASURES: Indicators of depressive disorder in transgenic mice, effect of antidepressant therapy on dexamethasone binding in transgenic mouse hippocampus, mouse behaviour, and glucocorticoid receptor activity. RESULTS: Transgenic mice showed no suppression of corticosterone with a dose of 2 mg per 100 g body weight dexamethasone. Treatment with amitriptyline reduced levels of corticotropin and corticosterone, increased glucocorticoid receptor mRNA concentrations and glucocorticoid binding capacity of several brain areas, and reversed behavioural changes. In vitro experiments also showed that desipramine increased glucocorticoid receptor mRNA. CONCLUSION: These transgenic mice have numerous neuroendocrine characteristics of human depression as well as altered behaviour. Many of these neuroendocrinologic and behavioural characteristics are reversed by antidepressants. The antidepressant-induced increase in glucocorticoid receptor activity may render the HPA axis more sensitive to glucocorticoid feedback. This new insight into antidepressant drug action suggests a novel approach to the development of new antidepressant drugs.     

Dexamethasone suppression test and the response to antidepressant depending on their central monoaminergic action in major depression

After 1 mg DST, 25 major depressive patients (DSM-III) received at random either a specific inhibitor of noradrenaline reuptake (Maprotiline) or an inhibitor of serotonin reuptake (Indalpine or Citalopram). After at least 3 weeks of treatment, no difference was found in treatment response between suppressors and non suppressors. This study is unable to confirm the usefulness of the DST in selection of treatment according to its central activity on serotonin or noradrenaline-reuptake.     

Dexamethasone suppression and energy balance: a study of anorexic patients

The performance of the dexamethasone suppression test (DST) was investigated in 45 female anorexic out-patients (cross-sectional study) and in nine female anorexic in-patients (longitudinal study). DST non-suppression was strongly associated with negative energy balance (low body weight and low Ponderal Index) but there was no significant association with the presence of affective or neurotic disturbance in these patients. These findings cast doubt on the value of the DST in the management of depressive illness.     

The benzodiazepine--GABA--chloride ionophore receptor complex: common site of minor tranquilizer action

The demonstration of specific recognition sites for benzodiazepines in the mammalian CNS has altered current thinking on the mechanisms of action of the benzodiazepines as well as the neurochemical events which are associated with anxiety. Recent studies suggest that the physiological regulation of the benzodiazepine receptor is far more complex than initially believed and includes a functional coupling to both a GABA receptor and an associated chloride ionophore. It now appears that a number of other psychopharmacologic agents, including minor tranquilizers other than the benzodiazepines as well as several convulsants and anticonvulsants, may exert their pharmacologic effects by affecting one or more regulatory sites on the benzodiazepine receptor complex. In addition to a number of drugs, at least one endogenous small molecular weight compound that has been isolated from the crude synaptosomal fraction of bovine cerebral cortex also appears to modulate this receptor complex.     

Dexamethasone suppression test: use of two different dexamethasone doses

The endocrinologic methods used in the dexamethasone suppression test (DST) for depression were examined, by employing two different doses of dexamethasone (0.5 or 1.0 mg) at 11 p.m. Nonsuppression to the 1.0 mg DST (plasma cortisol criterion value of 5 micrograms/dl) was seen in 33% of major depressives and in 15% of schizophrenics. A similar result was obtained with the 0.5 mg DST when 12 micrograms/dl was employed as the plasma cortisol criterion value. Plasma cortisol levels 33 hours postdexamethasone did not distinguish between major depressives and schizophrenics.     

Thyrotropin-releasing hormone induced thermogenesis in Syrian hamsters: site of action and receptor subtype

Early work in our laboratory has revealed the important role played by thyrotropin-releasing hormone (TRH) in the arousal from hibernation in Syrian hamsters. In the present study, we investigated the thermogenic mechanism of TRH in Syrian hamsters. Six to 10 female Syrian hamsters were used in the respective experiments. Intracerebroventricular (icv) injection of TRH elevated the intrascapular brown adipose tissue (IBAT) temperature (T(IBAT)) and rectal temperature (T rec) in Syrian hamsters. Thermogenic response of icv TRH was suppressed by bilateral denervation of the sympathetic nerve. Icv injection of TRH increased the norepinephrin (NE) turnover rate in IBAT without affecting the total serum triiodothyronine (T3) level. Moreover, TRH microinjections into the dorsomedial hypothalamus (DMH), preoptic area (PO), anterior hypothalamus (AH) and ventromedial hypothalamus (VMH) induced T(IBAT) and T(rec) increases. However, neither T(IBAT) nor T rec was affected by similar TRH administrations into the lateral hypothalamus and posterior hypothalamus. Interestingly, although TRH-induced hyperthermia was suppressed by pretreatment of anti-TRH-R1 antibodies, no changes were induced by anti-TRH-R2 antibodies. These results suggest that the sites of action of TRH associated with thermogenesis are probably localized in the DMH, PO, AH and VMH. In addition, TRH-induced thermogenesis is probably elicited by facilitation of the sympathetic nerve system via the central TRH-R1 irrelevant of T3.     

Dexamethasone suppression test and familial subtypes of unipolar depression

We have studied the suppression of plasma cortisol after dexamethasone (1 mg) and the peak post-dexamethasone cortisol values in 84 hospitalized patients with a diagnosis of primary unipolar depression. The non-suppressor responses in the three familial subgroups (Winokur) were: 11/22 in familial pure depressive disorder (FPDD), 21/49 in sporadic depressive disease (SDD) and 1/13 in depression spectrum disease (DSD) (FPDD vs. SDD, p less than 0.05; SDD vs. DSD, p less than 0.05). When considering the peak post-dexamethasone cortisol value, or the 8.30-9.00-hour values, the results in the DSD group were lower than in the other two groups (p less than 0.05). These results suggest a different behaviour of DSD as compared with FPDD and SDD.     

Dexamethasone suppression test and subcategories of DSM-III major depression

Among 37 patients with DSM-III major depression, the nonsuppression rate of the dexamethasone suppression test was significantly higher in patients with recurrent and melancholic major depression (83%) than in those with single episode and/or nonmelancholic major depression (31%).     

Antinociceptive action of GLYX-13: an N-methyl-D-aspartate receptor glycine site partial agonist

Inhibition of N-methyl-D-aspartate (NMDA)-mediated neurotransmission has been demonstrated to provide antinociceptive actions in a number of animal models of tonic and neuropathic pain. However, both competitive and noncompetitive NMDA receptor antagonists are ataxic at analgesic doses. Partial agonists and antagonists of the NMDA-associated glycine site have demonstrated antinociceptive actions at doses that are not ataxic. In this study, we present data showing that GLYX-13, an NMDA receptor, glycine-site, partial agonist, also is antinociceptive in the rat formalin model of tonic pain and in the rat constriction nerve injury model of neuropathic pain at doses not inducing ataxia.     

Dexamethasone suppression test in depression: association with duration of illness

ABSTRACT– Plasma cortisol response to 1 mg dexameihasone suppression test was investigated in 37 patients with primary major depressive illness. Non-suppression of plasma cortisol was found in 14 of 37 (38 %) patients. Duration of the index episode of illness was significantly shorter in the non-suppressors (11.1 ± 9.1 weeks) than in the suppressors (29.7 ± 25.6 weeks). The two groups were not distinguished by age, sex, polarity or severity of depressive symptoms. Eighty per cent of the non-suppressors (4/5) and 57 % of the suppressors (8/14) had severe life events or major difficulties in the 6 months preceding the onset of illness, but this difference failed to reach statistical significance.     

阴性和阳性精神分裂症地塞米松抑制试验比较

目的：了解了 和阳性精神分裂症ＨＰＡ轴调节功能的差异。方法：应用放射免疫法（ＲＩＡ）测试精神分裂症患者服用地塞米松前后的皮质醇水平,评价方法依Ｃａｒｏｌｌ方法进行,并引入新的地塞米松抑制试验（ＤＳＴ）统计方法,即血浆皮质醇绝对变化９ＡＣＰＣ０和血浆皮质醇相对变化（ＲＣＰＣ）。结果阳生精神分裂症ＤＳＴ前晨８时基础血浆皮质醇水平显著高于阴性精神分裂症,阳性精神分裂症ＤＳＴ后下竿４时和１１时两个时点血浆     

Dexamethasone suppression test in borderline personality disorder: impact of PTSD symptoms

The purpose of the present study was to investigate the impact of post-traumatic stress disorder (PTSD) symptoms on hypothalamic-pituitary-adrenal axis feedback regulation in 18 female patients with borderline personality disorder (BPD) and 21 healthy controls. Reduced feedback sensitivity was found in BPD patients with a low number of PTSD symptoms, while findings in the BPD group with a high number of PTSD symptoms did not differ from those in controls. The results suggest a hypo-suppression in the dexamethasone suppression test in BPD with few PTSD symptoms.     

Differential fornix ablations and the circadian rhythmicity of adrenal corticosteroid secretion

Suction ablations of the medial or lateral fornix were performed in order to transect selectively the medial corticohypothalamic tract (mcht) which originates in the anteroventral subiculum and travels in the lateral fornix terminating in the basal hypothalamus. The circadian rhythmicity of plasma adrenal corticosteroid levels was assessed in individual animals 1–2 weeks postoperatively. Ablation of the lateral fornix disrupted the periodicity of corticosteroid secretion which is normally synchronized with the light-dark cycle, whereas medial fornix ablation or neocortical ablation caused no such disruption. Group mean levels of plasma adrenal corticoids were higher in the lateral fornix-ablated animals than in the medial fornix-ablated, neocortically ablated, or intact control animals. These findings suggest that the anteroventral subiculum is important in the regulation of adrenal corticosteroid rhythmicity, and that it exerts an inhibitory influence upon corticosteroid release.     

Dexamethasone suppression test and depressive symptoms in bereaved children: a preliminary report

Eighteen bereaved children and adolescents were assessed using the dexamethasone suppression test (DST) and the Diagnostic Interview for Children and Adolescents 4 weeks following parental death. Thirty-nine percent had a positive (nonsuppressed) DST. DST-positive subjects reported more DSM-III-R depressive symptoms (6.3 +/- 2.9 vs. 3.9 +/- 2.7, means +/- SD) than DST-negative subjects. Most frequently reported symptoms included dysphoria, loss of interest, sleep disturbance, appetite disturbance, psychomotor disturbance, and morbid and suicidal ideation. Post-dexamethasone cortisol levels were significantly correlated with the total number of depressive symptoms and suicidal ideation.