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PubMed1997

Effect of adrenalectomy on cocaine facilitation of lateral hypothalamic self-stimulation.

An emerging body of evidence indicates that the adrenal hormone corticosterone modulates behavioral effects of abused drugs. Recently, it was reported that the self-administration and locomotor stimulatory effect of cocaine are blocked by adrenalectomy (ADX). In order to evaluate the effect of ADX on the brain reward system in general, and cocaine reward in particular, the effect of ADX on lateral hypothalamic self-stimulation (LHSS) and its facilitation by cocaine were investigated. Using curve-shift methodology, effects of cocaine (1.0, 3.0 and 10.0 mg/kg, i.p.) on the rewarding efficacy of brain stimulation were determined in ADX rats, with and without corticosterone supplementation, and compared with sham-operated controls. Results indicate that ADX does not affect LHSS or the facilitatory effect of cocaine. The divergence between these results and the results of cocaine self-administration studies is discussed in terms of the neuroanatomical and psychological processing of reward.

Adrenal Glands↗
PubMed1997

Adrenalectomy-induced granule cell death is predicated on the disappearance of glucocorticoid receptor immunoreactivity in the rat hippocampal granule cell layer.

In this study, we observed the changes of glucocorticoid receptor (GR)-immunoreactivity (ir) and cell death in the rat hippocampal granule cell layer at various periods after adrenalectomy (ADX). Our results revealed that all of the rats shortly after ADX showed a rapid loss of GR-ir and subsequent appearance of degenerating cells in the granule cell layer. One month after ADX, however, about 80% of the rats displayed a restoration of GR-ir and the absence of degenerating cells in the granule cell layer, and this phenomenon was successively noted for 6 months. Hippocampal structural destruction 3 and 6 months after ADX was found in about 20% of the rats with loss of GR-ir in the granule cell layer; the ADX rats with even weak GR-ir in this area had a normal hippocampus. The treatment of rats with synthetic GR agonist, dexamethasone, immediately after ADX prevented the loss of GR-ir and significantly reduced the number of degenerating cells in the granule cell layer. Our results clarified that granule cell death after ADX was necessarily accompanied by the disappearance of GR-ir in the granule cell layer, suggesting that ADX-induced granule cell death is predicated on the loss of GR-ir and that the presence of GR-ir in this area may be important for granule cell survival.

Adrenalectomy↗
PubMed1998

Effect of adrenalectomy on cocaine facilitation of medial prefrontal cortex self-stimulation.

Adrenalectomy (ADX) is known to block the acquisition of intravenous cocaine self-administration. A previous study therefore examined whether ADX decreases sensitivity of the 'brain reward system' in general, or its response to cocaine in particular, by measuring thresholds for intracranial self-stimulation with and without concurrent cocaine administration. ADX had no effect on thresholds for lateral hypothalamic self-stimulation (LHSS) and did not alter the cocaine dose-response curve for lowering the LHSS threshold. This result suggested that ADX does not affect sensitivity of the brain reward system. However, medial prefrontal cortex (MPFC) appears to be an important site in the mediation of cocaine reinforcing effects, and MPFC self-stimulation (MPFCSS) is mediated by a neural substrate that is largely independent of that which mediates LHSS. The present study therefore assessed whether ADX diminishes cocaine facilitation of MPFCSS. It was found that the threshold-lowering effect of cocaine (5.0, 10.0 and 20.0 mg/kg, i.p. ) did not differ between ADX rats maintained on 0.7% saline, ADX rats maintained on corticosterone (50 microg/ml) in 0.7% saline, and sham-operated controls. However, there was a trend toward desensitization of MPFCSS, itself, following ADX in the group that did not receive corticosterone supplementation. Based on this observation, and the similar responses of MPFCSS and cocaine self-administration to noncontingent priming stimulation, stress, and NMDA receptor antagonism, it is speculated that acquisition of MPFCSS and cocaine self-administration may be dependent upon a common sensitization process that is regulated by corticosterone.

Adrenalectomy↗
PubMed1998

Changes in IGF-1 receptors in the hippocampus of adult rats after long-term adrenalectomy: receptor autoradiography and in situ hybridization histochemistry.

Alteration of insulin-like growth factor-1 (IGF-1) receptor and its mRNA after long-term adrenalectomy (ADX) was studied in the hippocampus by in vitro receptor autoradiography and in situ hybridization histochemistry, respectively. Significantly, decreased levels of IGF-1 receptor and its mRNA was noted in the dentate and CA1-CA4 regions of the hippocampus of the ADX animals, suggesting that the level and expression of IGF-1 receptors in the hippocampus is influenced by adrenal hormones.

Adrenal Cortex Hormones↗
PubMed1999

Ultrastructural analysis of the hippocampus of adult rats after long-term adrenalectomy.

Removal of adrenal steroids modulates various functions in the brain. However, adrenalectomy (ADX) induced cell death in the hippocampal formation of the adult rat is a recently described phenomenon. We undertook this ultrastructural study on long-term adrenalectomized (5 months) rats to investigate the mode of cell death in the hippocampus. Our results showed apoptotic changes in the hippocampus. In addition we have observed other types of degeneration in the hippocampal neurons. The novel finding in this study is that different morphological patterns of cell death were evident both in the dentate gyrus and in the pyramidal areas, which may reflect different stages of the same death process.

Adrenalectomy↗
PubMed2000

The neurosteroid, 3alpha-androstanediol, prevents inhibitory avoidance deficits and pyknotic cells in the granule layer of the dentate gyrus induced by adrenalectomy in rats.

Testosterone (T), dihydrotestosterone (DHT), 3alpha-diol (5alpha-androstane-3alpha,17beta-diol), or vehicle was administered daily to gonadectomized, adrenalectomized male Long-Evans rats. Four days after adrenalectomy (ADX), animals were tested for inhibitory avoidance. Vehicle-treated rats had shorter latencies than 3alpha-diol-treated rats and non-corticosterone-depleted rats. All three androgens significantly reduced the number of pyknotic cells in corticosterone-depleted rats. Neurosteroids may mediate androgens' functional and morphological neuroprotective effects.

Adrenalectomy↗
PubMed2001

Clozapine-induced Fos-protein expression in rat forebrain regions: differential effects of adrenalectomy and corticosterone supplement.

Unlike classical antipsychotic drugs, clozapine activates the hypothalamo-pituitary-adrenal axis and induces a specific regional pattern of Fos-protein expression in the rat forebrain. Whether corticosterone plays a role in the clozapine-induced Fos response is the subject of this study. Some rats were adrenalectomized and in a number, including intact animals, a corticosterone pellet (100 mg s.c.) was implanted; after 1 week, a single dose of clozapine (20 mg kg(-1) i.p.) was administered. The clozapine-induced Fos response was not affected by adrenalectomy, apart from the nucleus accumbens shell, the subfornical organ and the supraoptic nucleus; there was an increased response in the nucleus accumbens shell, while other regions showed less Fos immunoreactivity. Implantation of the corticosterone pellet in both sham-operated and adrenalectomized animals, reduced the clozapine-induced Fos responses strongly in the hypothalamic paraventricular nucleus, the subfornical organ and possibly in the prefrontal cortex; in the supraoptic nucleus, this effect was seen only in intact animals. The effect of clozapine on plasma corticosterone levels was also diminished by supplemental corticosterone treatment. These results imply that the effects of clozapine are partially dependent upon hypothalamo-pituitary-adrenal axis integrity and activation. The efficacy of clozapine in the treatment of polydipsia and hyponatremia in chronic psychiatric patients may involve clozapine-mediated activation of the cellular activity in the subfornical organ.

Adrenalectomy↗
PubMed1994

Effectiveness and safety of laparoscopic adrenalectomy.

A laparoscopic approach was used to remove the adrenal gland in 7 patients with aldosterone-producing adenoma (Conn's disease), 2 with corticosteroid-producing adenoma (pituitary-independent Cushing's syndrome) and 2 with pheochromocytoma. The affected gland was on the right side in 3 patients and on the left side in 8. Mean operative time was 3 hours 10 minutes (range 140 to 370 minutes). The operation was uneventful in all patients and blood transfusions were never required. Mean postoperative hospitalization was 2.9 +/- 0.8 days (standard error). Only minimal doses of analgesics were used postoperatively. All patients returned to work within 10 days postoperatively (mean 8.4 +/- 1.2 days). Two months postoperatively no patient had clinical, biochemical or hormonal evidence of recurrent or persistent disease. We conclude that laparoscopic adrenalectomy is a safe and effective, minimally invasive approach for patients with benign adrenal neoplasms.

Adrenal Gland Neoplasms↗
PubMed1993

Adrenal autografts following bilateral adrenalectomy.

Bilateral adrenalectomy followed by immediate transplantation of adrenal slices into muscular tissue was performed in 7 patients with Cushing's disease and 1 with bilateral pheochromocytoma. Patients were followed for 1 to 7 years and only 1 had evidence of a functional graft (serum cortisol level at the lower limit of normality). Low levels of dehydroepiandrosterone sulfate, aldosterone and cortisol were found in the remaining patients. Acute stimulation with adrenocorticotropichormone did not increase either cortisol or aldosterone levels in any patient. We conclude that prospective studies are needed to elucidate factors that could improve the success of adrenal implantation, since the literature shows examples of functional grafts, while the majority of the cases are unsuccessful.

Adrenal Gland Neoplasms↗
PubMed1998

Distribution and concentration of urocortin, and effect of adrenalectomy on its content in rat hypothalamus.

We developed a specific and sensitive radioimmunoassay (RIA) for rat urocortin (rUcn) and investigated the tissue distribution and concentration of immunoreactive (IR-)Ucn in rats. Antiserum was obtained by immunizing rabbits with synthetic rUcn21-35 coupled with bovine thyroglobulin. 125I-[Tyr]18-rUcn19-37 was used as the tracer. The RIA detected synthetic rUcn1-40 as low as 0.4 fmol/tube, and did not cross-react with other corticotropin-releasing factor-related peptides. IR-Ucn was widely distributed in central nervous system, endocrine organs, and digestive system. Its concentration was highest in pituitary (11.0 +/- 1.36 pmol/g.w.w., mean +/- SEM, n=4). Reverse-phase HPLC revealed that hypothalamic IR-Ucn had similar chromatographic mobility to synthetic rUcn1-40. However, bilateral adrenalectomy did not influence the hypothalamic IR-Ucn content. Our results suggest that Ucn may play important roles in various tissues in normal rats, but not behave as a hypothalamic hypophysiotropic factor in mediating adrenocorticotropin secretion in adrenalectomized rats.

Adrenal Glands↗
PubMed1988

Effect of frusemide on urinary kallikrein excretion in the conscious rat: influence of adrenalectomy and DOCA treatment.

The effect of subcutaneous frusemide administration on urinary kallikrein excretion was studied in the conscious state, in control, adrenalectomized and DOCA-treated adrenalectomized rats. Frusemide increased urinary kallikrein excretion in the three groups of rats. Urine volume and urinary sodium and potassium excretions were also increased. These responses were however suppressed by adrenalectomy but normalized by DOCA treatment. It is concluded that frusemide's stimulation of urinary kallikrein excretion in the conscious rat is modulated by mineralocorticoid activity.

Adrenalectomy↗
PubMed2001

Effects of adrenalectomy and hormone replacement on B6C3F1 mice fed a high-fat diet.

Bilateral adrenalectomy (ADX) causes decreased circulating leptin in both obese and lean mice. It remains unclear whether the decreased plasma leptin after ADX is due to decreased adipose tissue or is due to decreased circulating glucocorticoids. The present experiment was performed to test the hypothesis that the absence of glucocorticoids from circulation is sufficient to decrease circulating leptin. Sixty-four adult male B6C3F1 mice were individually housed and fed either Purina rat chow or an experimental diet. After 6 weeks, mice fed the experimental diet gained more weight than mice fed the control diet. Each dietary group was then subdivided into four groups: ADX with cholesterol replacement (ADX-CHOL), ADX with corticosterone (CORT) replacement (ADX+CORT), ADX with aldosterone (ALDO) replacement (ADX+ALDO), and sham operation (SHAM). Two days after surgery, mice were killed and exsanguinated and the carcasses were prepared for gravimetric analyses. Blood was collected and centrifuged and the plasma was assayed for leptin, CORT, and ALDO. Blood glucose was determined using whole blood taken before centrifugation. There was no difference in body weight due to ADX after 2 days. Mice fed the experimental diet had higher circulating leptin than those fed the control diet. The ADX+CORT groups (both experimental and control diets) had higher plasma leptin concentrations than the other groups. No differences were observed between ADX-CHOL and SHAM groups. These results suggest that circulating leptin is not directly controlled by glucocorticoids. The effect of ADX on circulating leptin reported by others may be the consequence of decreased adiposity.

Adrenal Cortex Hormones↗
PubMed2001

Adrenalectomy eliminates the extinction spike in autoshaping with rats.

Experiment 1, using rats, investigated the effect of adrenalectomy (ADX) on the invigoration of lever-contact performance that occurs in the autoshaping situation after a shift from acquisition to extinction (called the extinction spike). Groups of rats with ADX or sham operations were trained under spaced and massed conditions [average intertrial intervals (ITI) of either 15 or 90 s] for 10 sessions and then shifted to extinction. ADX did not affect acquisition training but it eliminated the extinction spike. Plasma corticosterone levels during acquisition were shown in Experiment 2 to be similar in rats trained under spaced or massed conditions. Adrenal participation in the emotional arousal induced by conditions of surprising nonreward (e.g., extinction) is discussed.

Adrenalectomy↗
PubMed2002

The effects of adrenalectomy and aldosterone replacement in transgenic mice expressing antisense RNA to the type 2 glucocorticoid receptor.

Bilateral adrenalectomy (ADX) either prevents or attenuates obesity in several animal models. Mice that express an antisense RNA to the glucocorticoid receptor (GCR) are obese. The present study was conducted to examine the effects of ADX and aldosterone (ALDO) replacement on the rate of weight gain and body composition of mice bearing an antisense GCR gene construct. Twenty-eight male transgenic mice bearing the antisense GCR construct and 16 male B6C/3F1 mice were either bilaterally ADX or given sham operations. At the time of surgery, some of the ADX mice and all of the sham-operated mice were implanted with 100-mg cholesterol (CHOL) pellets inserted subcutaneously in the subscapular region. The remaining ADX mice were implanted with 100-mg 1% w/w ALDO pellets using CHOL as vehicle. All mice were returned to their home cages for 2 weeks. They were then decapitated and the blood was collected for corticosterone, ALDO, insulin, and leptin radioimmunoassay. Carcasses were eviscerated and prepared for gravimetric analyses, including bomb calorimetry. ADX resulted in a significant drop in carcass fat in both transgenic and wildtype groups. ALDO prevented the decrease in carcass fat in both groups. Two weeks after ADX, transgenic mice were as fat as sham-operated wildtype controls, whereas both sham-operated and ALDO-treated transgenic groups were significantly fatter. Despite observing a reliable decrease in carcass fat following ADX, no corresponding decrease in circulating leptin was found.

Adrenal Cortex Hormones↗
PubMed1997

Adrenalectomy lowers the body weight set-point in rats.

In order to evaluate the impact of a complete depletion of glucocorticoids on rats' body weight set-point, rats were adrenalectomized, and their set-points were estimated before, and after surgery. Body weight set-points were obtained from a quantitative behavioral method based on the rats' food-hoarding response to weight deficit. In addition, body fat contents were measured in vivo using a total body electrical conductivity analyzer (TOBEC). The hoarding of food showed that adrenalectomized rats had significantly lower body weight set-points than the sham-operated controls (337 +/- 11 g vs. 385 +/- 8 g) and were also significantly lighter. TOBEC measurements showed that the sham-operated control rats had a higher body fat content than the adrenalectomized rats ( 16.7 +/- 1.1% vs. 10.2 +/- 1.2%). The present study demonstrates that adrenalectomy lowers the body weight set-point in rats, suggesting that the concentrations of glucocorticoid hormones, and in turn, the hypothalamic corticotrophin releasing hormone (CRH) participates in the adjustment of the body weight set-point.

Adrenalectomy↗
PubMed1996

Laparoscopic adrenalectomy.

Laparoscopic adrenalectomy has become a viable option for removal of adrenal pathology and is becoming preferred over the conventional technique. With the conventional technique, many approaches are available, which vary according to pathology, diameter of the adrenal mass, location of the lesion, and patient morphology. Knowledge of anatomy is essential, because careful hemostasis and delicate tissue handling are necessary to make adrenal surgery a success.

Adrenal Gland Diseases↗
PubMed2002

Comparison study on two different accessing methods for retroperitoneoscopic adrenalectomy.

OBJECTIVES: To compare, in a retrospective nonrandomized study, two retroperitoneal laparoscopic access methods for treatment of adrenal tumors: direct needle insufflation with balloon dissection and finger-assisted dissection without balloon dissection. METHODS: The operative data from 120 consecutive patients undergoing retroperitoneoscopic adrenalectomy (RA) for benign adrenal tumors were reviewed. The operative outcomes of 70 RAs accessed by direct needle insufflation and balloon dissection were compared with another 50 RAs accessed by finger dissection without balloon dissection. The RA surgical parameters for tumors with different laterality, pathologic features, and size were also analyzed. RESULTS: The operative time in the finger dissection group was shorter (118 +/- 11 minutes) compared with that in the balloon dissection group (143 +/- 21 minutes; P = 0.03). The surgical parameters, including incidence of peritoneal perforation, intraoperative blood loss, time to oral intake, analgesic requirement, postoperative hospital stay, and convalescence, did not differ between the groups. For tumors greater than 5 cm, the operative time increased to 220 +/- 30 minutes compared with 132 +/- 31 minutes for tumors 5 cm or less (P = 0.02). The finger and balloon dissection methods had similar operative times for tumors larger than 5 cm (218 +/- 10 versus 224 +/- 15 minutes). No additional morbidity regarding the recovery time was noted in the finger dissection group compared with the balloon dissection group. CONCLUSIONS: Finger dissection appears to be a more efficient and equally effective access method for RA compared with balloon dissection. We suggest that balloon dissection may not be required for RA in patients not excessively obese.

Adrenal Gland Neoplasms↗
PubMed1998

Calbindin-D28k- and astroglial protein-immunoreactivities, and ultrastructural differentiation in the prenatal rat cerebral cortex and hippocampus are affected by maternal adrenalectomy.

Maternal adrenal steroid hormones have been proven to be crucial for lung and adrenal prenatal maturation. These hormones mediate the effects of prenatal stress crossing the placenta and influencing the development of the hypothalamus-pituitary-adrenal axis of fetuses. In the present study, we have compared the prenatal development of fetuses from adrenalectomized mothers (ADX group) and from sham-operated mothers. We have used immunohistochemistry for calcium binding-protein Calbindin-D28k, astroglial proteins vimentin and glial fibrillary acidic protein (GFAP), and the ultrastructural differentiation of the cerebral cortex and hippocampus to measure putative differences. The ontogeny of the Calbindin-D28k immunoreactivity was delayed, as transient Calbindin-positive neuronal populations in the ADX group disappeared later during development as compared to that of control animals both in cerebral cortex and hippocampus; cell counts revealed that ADX animals had a significantly higher number of Calbindin-positive cells than controls in the cerebral cortex, while that number was lower in ADX fetuses' hippocampus. Cerebral cortex of ADX animals also had a scattered distribution of stained cells compared with controls, while the hippocampi of the ADX animals had an impaired migration of marginal zone interneurons. No GFAP immunoreactivity was found in the studied prenatal stages. Instead, vimentin-immunoreactivity appeared more profusely distributed throughout the cerebral cortex, in the ADX group than in control animals. At the ultrastructural level, no remarkable differences were found before E20, when a higher undifferentiation in the ADX group, in both cerebral cortex and hippocampus, was evident. The results show for the first time the vulnerability of the prenatal rat brain to maternal adrenalectomy and the necessity of maternal glucocorticoids for encephalic development.

Adrenalectomy↗