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Biomedical subjects

M T Lowy

Publications and source records attributed to M T Lowy.

At least 37 records · Page 2Linked to original sources
PubMed1989

Selective reduction of striatal type II glucocorticoid receptors in rats by 3,4-methylenedioxymethamphetamine (MDMA).

A single 20 mg/kg dose of 3,4-methylenedioxymethamphetamine (MDMA) administered to rats markedly decreased serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in hippocampus, frontal cortex and striatum seven days following injection. MDMA also significantly decreased type II glucocorticoid receptor levels in the striatum, but not in hippocampus or frontal cortex. Since no difference in basal serum corticosterone levels was observed between the two groups, MDMA may decrease striatal type II glucocorticoid receptors via a corticosterone-independent mechanism.

3,4-Methylenedioxyamphetamine↗
PubMed1988

Stimulation of serum cortisol and prolactin secretion in humans by MK-212, a centrally active serotonin agonist.

The effects of MK-212 [6-chloro-2-(1-piperazinyl)-pyrazine] (10, 20, and 40 mg, orally), a centrally acting serotonin (5-HT) receptor agonist and placebo, on serum cortisol, prolactin, and growth hormone levels were studied in eight healthy men over 3-hr. MK-212 produced a dose-related increase in serum cortisol levels, with the 20- and 40-mg doses producing significant elevations. Serum prolactin levels were significantly elevated only by the 40-mg dose. Serum GH levels were not significantly modified by any dose of MK-212. The cortisol and prolactin responses to the 40-mg dose of MK-212 were positively correlated (rho = + 0.85, p less than 0.02). MK-212 was generally well tolerated by the subjects. Headache and nausea were observed at the higher doses, but did not appear to be related to the increase in serum cortisol and prolactin levels. MK-212 may stimulate the secretion of cortisol and prolactin in humans via a serotonin (5-HT2) receptor mechanism and may be a valuable tool with which to study 5-HT receptor sensitivity in humans.

Adult↗
PubMed1988

Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: relationship to the dexamethasone suppression test.

The effect of in vivo (1 mg) and in vitro (10(-7)-10(-10) M) dexamethasone administration on mitogen-induced lymphocyte proliferation was examined in drug-free depressed patients, nondepressed psychiatric patients, as well as normal controls, and was related to the results of a standard overnight Dexamethasone Suppression Test (DST). The effect of oral dexamethasone administration was also examined for its effect on lymphocyte cytosolic glucocorticoid receptor content. Oral dexamethasone administration significantly decreased both phytohemagglutinin (PHA) and concanavalin A (Con-A) induced lymphocyte proliferation, as well as glucocorticoid receptor number in suppressors, whereas dexamethasone failed to decrease these responses in nonsuppressors. Nonsuppressors had significantly lower serum dexamethasone levels compared to suppressors at both 8:00 AM and 4:00 PM. However, when differences in serum dexamethasone levels were covaried out, there were still significant differences between suppressors and nonsuppressors on the dexamethasone-induced mitogen changes, but the changes in glucocorticoid receptor content were no longer significant. In vitro incubation of lymphocytes with dexamethasone produced a dose-related decrease in mitogenesis, which was not different between the depressed and nondepressed groups. However, at physiologically relevant concentrations of dexamethasone (10(-9)-10(-10) M), nonsuppressors as compared to suppressors were more resistant to the immunosuppressive effects of in vitro dexamethasone on the Con-A response. The inhibitory effect of in vitro dexamethasone on Con-A-stimulated lymphocytes was positively correlated with basal 4:00 PM cortisol values. In conclusion, in vitro techniques are useful probes to assess glucocorticoid sensitivity in depression. The present results also further support the hypothesis that glucocorticoid insensitivity is associated with DST nonsuppression.

Adult↗
PubMed1988

Platelet MAO activity and the cortisol response to dexamethasone in major depression.

Previous studies have sometimes found a positive relationship between platelet monoamine oxidase (MAO) activity and dexamethasone nonsuppression in depressed patients. To assess this relationship in more detail, we examined the association between these two biological variables in unmedicated depressed patients. A positive correlation between platelet MAO activity and 8:00 AM serum cortisol levels following an overnight dexamethasone test (1 mg) was observed. The relationship between high and low platelet MAO activity (median split) and suppression of serum cortisol levels was also significant. These relationships were stronger in bipolar patients. Multiple regression revealed that postdexamethasone 8:00 AM dexamethasone levels and platelet MAO activity were independent predictors of the 8:00 AM cortisol levels following dexamethasone. The possibility that platelet MAO activity may be a peripheral marker of brain serotonergic activity which in turn may affect various aspects of the hypothalamo-pituitary-adrenal axis activity, is discussed. We also found that all nine depressed patients studied greater than or equal to 15 days after admission were suppressors. Platelet MAO activity, but not 8:00 AM pre- or postdexamethasone serum cortisol, was related to the severity of depression.

Adult↗
PubMed1988

Plasma cortisol and depression in pathological gamblers.

Basal serum cortisol and dexamethasone suppression test (DST) results were studied in 21 pathological gamblers who varied on the Beck Depression Inventory and selected scales of the Minnesota Multiphasic Personality Inventory, which had previously been shown to be related to depression in gamblers. All subjects were suppressors on the DST. There was a significant relationship between fluctuation in 08.00 h and 16.00 h basal cortisol levels and the psychological measures, suggesting a subtype of pathological gambler with potential clinical significance.

Adult↗
PubMed1987

Dexamethasone bioavailability: implications for DST research.

The bioavailability of dexamethasone (DEX) has recently been demonstrated to be a critical factor in determining Dexamethasone Suppression Test (DST) status in psychiatric patients. This brief review focuses on several aspects of DEX bioavailability as they relate to the use of the DST in neuroendocrine research. Several methodologies, including radioimmunoassay, high-performance liquid chromatography, and gas chromatography-mass spectrometry are available for quantification of DEX in biological fluids, although few detailed comparisons between methods have been reported. Surprisingly, little systematic research on the metabolism of DEX has been reported, but it appears that hepatic rather than renal mechanisms are the major source of DEX elimination. The marked variability in serum DEX levels following oral administration in psychiatric patients is also observed in normal controls and patients with Cushing's syndrome. A variety of drugs can modify serum DEX levels and thereby after the effectiveness of DEX in suppressing serum cortisol levels. Simultaneous measurement of serum DEX and cortisol levels appears to be necessary for the appropriate evaluation of DST results. This procedure may help explain many of the inconsistencies in recent DST research.

Biological Availability↗
PubMed1987

5-Hydroxytryptophan-induced cortisol response and CSF 5-HIAA in depressed patients.

To determine if the enhanced cortisol response to oral administration of the serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP) that has been reported in unmedicated depressed and manic patients might be related to brain monoaminergic metabolism, the authors assessed correlations between 5-HTP-induced cortisol response and CSF in nine depressed patients. They found a significant negative correlation with CSF levels of 5-hydroxyindoleacetic acid, a 5-HT metabolite, but not with CSF levels of other monoamine metabolites. This finding is consistent with the hypothesis that low presynaptic brain serotonergic activity may be related to enhanced cortisol response to 5-HTP in depressed patients.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Dexamethasone suppression test abnormalities in multiple sclerosis: relation to ACTH therapy.

We studied the 1-mg overnight dexamethasone suppression test (DST) in patients with MS. In about 50% of patients, serum cortisol did not fall below 5.0 micrograms/dl. This percentage was similar in patients with major depression, but contrasted to 11% in normal controls. MS nonsuppressors were not more depressed than suppressors; dexamethasone bioavailability may have contributed because nonsuppressors had lower serum dexamethasone levels than suppressors. Suppressors improved in the week following ACTH therapy; nonsuppressors did not. Furthermore, serum dexamethasone values correlated positively with clinical response to ACTH treatment. The DST may be a useful neuroendocrine test of glucocorticoid sensitivity in MS patients.

Adrenocorticotropic Hormone↗
PubMed1985

Effects of 2% sodium chloride imbibition on various opiate related hyperphagic conditions.

Dynorphin is one of the most potent appetite stimulants among the endogenous opioids. In this study, we describe the anorexic effects of 5 days of forced 2% NaCl drinking in rats, a regimen which depletes vasopressin as well as dynorphin in the neurohypophysis. Feeding induced by direct activation of kappa-opioid receptors with ketocyclazocine was unaffected by the NaCl regimen. However, 2% NaCl imbibition reduced 2-deoxy-D-glucose (2-DG) induced feeding by 65% and spontaneous nocturnal feeding by 38%. Feeding subsequent to 24 hour food deprivation was not decreased. Naloxone-resistant hyperphagia induced by insulin and spontaneous daytime feeding were also not reduced. The combination of naloxone (3.0 mg/kg) and the NaCl regimen produced an additional 50% reduction in 2-DG induced feeding and an extra 40% decrease in nocturnal feeding. Naloxone, given with 2% NaCl to food deprived animals, retained its appetite suppressing activity, indicating that the NaCl regimen did not deplete the endogenous opioid which mediates food deprivation hyperphagia. These results demonstrate that 2% NaCl imbibition suppresses certain opioid mediated hyperphagias. However, the failure of 2% NaCl to affect all of the naloxone-sensitive types of feeding and the independence of naloxone-sensitive and NaCl-sensitive components suggests that NaCl drinking does not deplete dynorphin in the brain areas which mediate opiate-sensitive hyperphagias.

Animals↗
PubMed1985

Naltrexone fails to suppress spontaneous locomotor activity in hamsters.

The increased spontaneous locomotor activity (SLMA) of rats exposed to a novel environment is decreased by opiate antagonists. In the present study, naltrexone (1.0-40 mg/kg) failed to reduce the SLMA of hamsters exposed to the novel environment of activity cages. The SLMA of another group of untreated hamsters declined following 4 consecutive exposures to the activity cages. Thus, the novelty-induced increase in hamster SLMA is not sensitive to opiate antagonism. The differential sensitivity of rats and hamsters to opiate effects on activity and feeding may be due to the presence of an opiate-sensitive hibernation system in hamsters.

Animals↗
PubMed1985

Opioid modulation of feeding behavior following forced swimming exercise in male rats.

Adult male rats were subjected to an acute bout of swimming exercise for 50 min during the early morning or late afternoon. Compared to nonexercised controls, all exercised groups showed an initial approximately 2-hr period of increased feeding (period I hyperphagia). A 50-min period of sham swimming (wading in water) was followed by period I hyperphagia but not period II hypophagia. Opioid modulation of period I hyperphagia was indicated by the ability of naltrexone to antagonize, in a dose-dependent manner, the postexercise hyperphagia. Furthermore, plasma concentrations of immunoreactive B-endorphin (Ir-B-ep) were increased during period I following exercise. Opioid modulation of the period II hypophagia was equivocal. Plasma Ir-B-ep was not altered in period II, and naltrexone did not modify period II hypophagia. The ability of 2-deoxy-D-glucose to induce feeding was slightly depressed (p less than 0.05) during period II after exercise, and the ability of exogenous insulin to induce feeding was not changed. These differential feeding responses to 2-deoxy-D-glucose (opioid-mediated) and insulin (relatively opioid-independent) suggest that an opioid deficiency may exist during period II and contribute to the hypophagia.

Animals↗
PubMed1985

Glucocorticoid receptors in depression: relationship to the dexamethasone suppression test.

Cytoplasmic glucocorticoid receptor content wa quantitated in lymphocytes from unmedicated depressed patients and control subjects before and after a standardized dexamethasone suppression test. Depressed patients (N = 11) had significantly lower (32%) basal cytoplasmic glucocorticoid receptor content than the control group (N = 14). Suppression of serum cortisol (5.0 micrograms/dl or less) in both control and depressed subjects (N = 16) following dexamethasone (1 mg) was associated with a decrease in lymphocyte cytoplasmic glucocorticoid receptor number, whereas no such change occurred in cortisol nonsuppressors (N = 9). Changes in receptor concentration were positively correlated with postdexamethasone serum cortisol levels and with the inhibitory effect of dexamethasone on mitogen-induced lymphocyte proliferation.

Adult↗
PubMed1984

Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone.

Approximately 50% of depressed patients are resistant to the cortisol-suppressing effect of dexamethasone. To determine if glucocorticoid resistance could be a more generalized phenomenon in depressed patients, mitogen stimulation tests were performed on lymphocytes from 12 depressed patients and 12 control subjects before and after dexamethasone administration. Suppression of serum cortisol following administration of 1 mg of dexamethasone in four depressed patients and 11 control subjects was associated with a decreased lymphoproliferative response, but no such change occurred in the eight depressed patients and the single control subject who did not suppress cortisol. The dexamethasone-induced changes in the mitogen responses were positively correlated with the highest postdexamethasone serum cortisol values.

Adult↗
PubMed1984

Opioids, feeding, and anorexias.

This review summarizes recent work that focuses on the role of endogenous opioids (EOs) and opiate receptors in the control of food intake. Although the anorexic effect of opiate antagonists are now well accepted, the exact EO, site(s), and mechanism(s) of action remain to be established. However, accumulating evidence suggests that dynorphin, an endogenous ligand for kappa-type opiate receptors, is an important regulator (stimulant) of appetite. The roles of other EOs, such as beta-endorphin, are less clear. EOs appear to be involved in maintaining normal feeding behavior and are likely responsible for the overconsumption of fat in genetically obese and stressed subjects. Opiate antagonists block overconsumption of palatable foods, thus offering a promising approach to weight reduction for some overweight individuals. Anorexias may follow from a deficiency of kappa-type opioid activity, and surprisingly, can also result from excess opioid activity. Indeed, opiate antagonists of the mu type (naloxone) can enhance eating and weight gain in certain anorexic conditions. Therefore, it appears that excess opioid agonist activity may result in hyperphagia or anorexia (depending on the opiate receptor type). Finally, opiate antagonists may help normalize both types of pathological feeding states.

Animals↗
PubMed1984

Central and peripheral anti-inflammatory actions by clonidine and a structurally related imidazoline analog.

Systemic (i.p. and p.o.) administration of clonidine significantly reduced the acute inflammatory swelling of the rat paw produced by carrageenin, histamine and serotonin. Clonidine did not reduce carrageenin swelling when given i.c.v. Intraperitoneal administration of a structural analog of clonidine, 2-(2-methyl-4- chlorophenylamine ) -2-imidazoline (CDMI), was only effective against carrageenin swelling. CDMI was 10 times more effective when given centrally (i.c.v.) than when given systemically (i.p. or p.o.). The slopes of the individual dose-response curves were not significantly different which suggested a common mechanism of action. However, although adrenalectomy did not reduce the anti-inflammatory activity of i.p. CDMI, i.c.v. CDMI was ineffective in adrenalectomized rats. These results indicate that imidazolines represent a unique class of anti-inflammatory agents with actions mediated both peripherally and centrally.

Adrenalectomy↗
PubMed1983

Stimulation of food intake following opiate agonists in rats but not hamsters.

The proposed mu and kappa opiate receptor agonists morphine and ketocyclazocine, as well as meperidine, were compared for their ability to stimulate feeding and drinking by male rats and hamsters that were not deprived of food or water. Morphine (8.0 mg/kg) and ketocyclazocine (0.5-4.0 mg/kg), but not meperidine (0.5-64.0 mg/kg), increased 3-h food intake by rats. By 6 h the hyperphagic responses were less pronounced. However, 6-h water intake was increased by all three agonists. In contrast to rats, hamsters failed to increased food or water intake over an 8-h period following morphine (6.25-800 mg/kg), ketocyclazocine (0.25-16.0 mg/kg), or meperidine (1.0-128 mg/kg) administration. Thus, kappa or mu opiate receptors may mediate the observed hyperphagic effect of opiate agonists on rat food intake. In addition, these results are consistent with our earlier suggestion that hamsters lack an opiate-sensitive feeding system.

Animals↗