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Biomedical subjects

D Naber

Publications and source records attributed to D Naber.

At least 127 records · Page 7Linked to original sources

Endorphins in the cerebrospinal fluid of psychiatric patients.

In this paper we have reported the results of studies in psychiatric patient groups using the strategy of measuring opioid activity and beta-endorphin (ir) in CSF. Our findings do not lend support to the notion of excess endorphin activity in schizophrenia, but rather suggest the possibility of a decrease in endogenous opioid activity in some schizophrenic patients. In affectively ill patients our data suggest that there may be a relative change in endogenous opioid system activity across state change in manic-depressive illness. Who also found a relationship between nurses' ratings of anxiety and CSF opioid activity in depressed patients, although it is unknown whether this directly relates to the pathophysiology of this symptom, or is related to stress response. The relationship between CSF opioid activity and HPA axis activity, as reflected by urinary free cortisol excretion, supports the notion of important physiologic relationships between these systems and raises the issue of a role for the endogenous opioid system in the abnormal activation of this system in depression. Finally, the finding of increased CSF opioid activity in anorexia nervosa patients when a minimum weight coupled with data relating endogenous opioids to eating behavior raises interesting questions regarding a possible involvement of the endogenous opioid system involvement in this illness.

Adult↗

Effect of lithium on circadian neurotransmitter receptor rhythms.

Chronic lithium administration significantly changes characteristics of the circadian rhythms in rat brain alpha- and beta-adrenergic, muscarinic acetylcholine, dopamine, opiate, and benzodiazepine receptors. There are changes in the timing of the peak number of receptors (phase-position), in the amplitude of the rhythms, and in the 24-hour mean number of receptors. The circadian rhythm in the number of forebrain alpha- and beta-adrenergic and benzodiazepine receptors is abolished. The phase-position of forebrain acetylcholine and opiate receptors and striatal benzodiazepine receptors is delayed. As the rhythms of the dopamine receptor number and alpha-melanocyte-stimulating hormone secretion become bimodal, their phase positions are difficult to evaluate. The mean number of forebrain alpha- and beta-adrenergic, acetylcholine, opiate, and striatal benzodiazepine receptors increases. The mean number of forebrain benzodiazepine and striatal dopamine receptors and the mean concentration of alpha-melanocyte-stimulating hormone decreases. Lithium has profound effects on each of the receptor rhythms measured. Slowing and altering circadian rhythms may contribute to the therapeutic effects of chronic lithium treatment in affective disorders.

Animals↗

Cerebrospinal fluid opioid activity in anorexia nervosa.

The authors found higher levels of CSF opioid activity, determined by radioreceptor assay, in patients with anorexia nervosa who were severely underweight than in 1) the same patients after weight restoration and 2) normal controls. Another group of patients who had chronic anorexia nervosa but were not severely underweight had normal levels of CSF opioid activity. Endogenous opioid systems have been shown to be related to eating behavior and metabolic regulation in animals. The association between decreased weight and increased CSF opioid activity observed by the authors may be a compensatory response to weight loss or may be etiologically related to anorexia nervosa.

Adult↗

Clinical studies of the endogenous opioid system.

The role of the endogenous opioid system in humans was studied using three clinical research strategies. High doses of the opiate antagonist naloxone (up to 4 mg/kg) were administered to normal volunteers. Dose-dependent increases in self-ratings of tension-anxiety and anger-hostility were observed, supporting the hypothesized involvement of the endogenous opioid system in the modulation of human mood and feelings of well-being. Accompanying dose-dependent increases in systolic blood pressure and respiratory rate were found, suggesting that the lower doses of naloxone utilized in previous clinical studies were not sufficient to block the endogenous opioid system. CSF opioid activity in psychiatric patients and normals was measured using a sensitive radioreceptor assay developed by the authors. Results suggest diminished endogenous opioid system activity in some schizophrenics, and a relationship between opioid activity and state change in manic-depressive illness and anorexia nervosa. A complex but consistently observed relationship between ratings of anxiety and CSF opioid activity in normals and patients is consistent with basic science and clinical data suggesting interactions between CNS noradrenergic and opioid systems. General surgery was used as a strategy for studying the relationship of the endogenous opioid system to stress in humans; robust increases in levels of plasma beta-endorphin immunoreactivity accompanying surgical stress and an inverse relationship between patient levels of plasma beta-endorphin immunoreactivity and postoperative analgesic requirement were observed. These data support the involvement of the endogenous opioid system in the human stress response and suggest that hormonal stress response and endogenous opioid system activity may relate to human endogenous analgesic mechanisms.

Adolescent↗

Circadian and seasonal rhythms in alpha- and beta-adrenergic receptors in the rat brain.

Circadian rhythms in the numbers of alpha- and beta-adrenergic receptors exists in the rat forebrain and hypothalamus. These rhythms are endogenous as they persist in the absence of time cues. The alpha- and beta-receptor rhythms differ both in their shapes (wave form) and in the timing (phase) of the peak numbers. In the course of the year, there are shifts in the timing of both alpha- and beta-receptor peaks. Circadian rhythms in synchronizing both the synaptic events and the behaviors related to them to the photoperiod of the natural environment.

Animals↗

Circadian rhythm in rat brain opiate receptor.

To investigate diurnal variations in opiate receptor binding, the amount of specifically bound [3H]naloxone was measured at 4-h intervals across a 24-h period in the forebrains of rats that had been housed under a controlled light--dark cycle (lights on from 07.00 to 19.00 h) for 3 weeks. A significant rhythm with a peak at 22.00 h was found, the amplitude was 46--78%. In the absence of time cues, this circadian rhythm persisted with a peak at 02.00--06.00 h and an amplitude of 88%. Scatchard analysis indicated that the differences in binding throughout the day were due not to changes in affinity, but to changes in the number of binding sites.

Animals↗

Naloxone effects on beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG in plasma of normal volunteers.

8 mg of naloxone were administered IV to 14 normal volunteers in a placebo-controlled, double-blind experiment. Plasma levels of beta-endorphin, cortisol, prolactin, growth hormone, HVA and MHPG were determined before and 45 min after administration. Naloxone elicited significant increases in cortisol and MHPG but did not change plasma levels of the other compounds. In an additional experiment on two subjects, 20 mg of naloxone caused elevations of beta-endorphin as well as of cortisol. This parallel increase indicates that the linkage between the secretion of beta-endorphin and ACTH/cortisol may be dose-dependent. The increase in MHPG is in agreement with the hypothesized association of noradrenergic hyperactivity and opiate withdrawal.

Adult↗

Effect of carbamazepine on CSF opioid activity; relationship to antidepressant response.

Carbamazepine, a drug useful in the treatment of trigeminal neuralgia and temporal lobe epilepsy, has recently been found to have positive psychotropic effects in patients with manic and depressive illness. The possible effect of carbamazepine on opioid activity in cerebrospinal fluid (CSF) were assessed in patients with affective disorders using a radioreceptor assay that detects total opioid binding activity. No effect of carbamazepine was noted on CSF total opioid activity, although conclusions about its possible effects on discrete opiate systems must await other methodologies. Initial medication-free levels of opioid activity were positively correlated with the degree of antidepressant response to carbamazepine.

Carbamazepine↗

Sleep deprivation: effects on circadian rhythms of rat brain neurotransmitter receptors.

Specific binding of ligand to rat forebrain alpha- and beta-adrenergic, muscarinic cholinergic, opiate, benzodiazepine, and striatal dopamine receptors was measured at 4-hour intervals during the last 13 hours of a 24-hour sleep deprivation period, and during the first 11 hours of the recovery sleep period. In non-sleep-deprived controls a 24-hour rhythm in binding was evident. The minor differences between the sleep deprivation group and the control group consisted mainly in a reduced amplitude of the 24-hour rhythm under the sleep deprivation schedule. The results indicate that neither the 24-hour forced locomotion nor the subsequent prominent sleep rebound is accompanied by marked changes in the number of neurotransmitter receptors and their circadian rhythms.

Animals↗

Relationship between urinary free cortisol and CSF opioid binding activity in depressed patients and normal volunteers.

We investigated the relationship between hypothalamic-pituitary-adrenal (HPA) activity, as measured by 24-hour mean urinary free cortisol (MUFC), and cerebrospinal fluid (CSF) opioid activity in patients with major affective disorder and normal volunteers. Among depressed patients, but not normal volunteers, mean 24-hour urinary cortisol values were significantly correlated with CSF opioid activity measured by radioreceptor assay, but were not significantly correlated with beta-endorphin immunoreactivity measured by radioimmunoassay. MUFC, as expected, was significantly higher in depressed patients than in normal volunteers. Mean values of CSF opioid activity and beta-endorphin immunoreactivity did not differ significantly in the two groups. The positive opioid-MUFC correlation found in the depressed group appeared to depend on patients who were cortisol hypersecretors. These data, using relatively crude measures of cortisol and opioid activity, are suggestive of a relationship between these two systems, particularly under "activated" conditions such as those observed in depression.

Adult↗

Ethanol increases opioid activity in plasma of normal volunteers.

The effect of acute ethanol administration on plasma levels of beta-endorphin-immunoreactivity and opioid activity was measured in 4 normal volunteers. 60 min following ethanol consumption opioid activity levels, measured by radioreceptorassay, increased significantly with peak rises of more than 400%; levels of beta-endorphin-immunoreactivity did not change significantly. These results are compatible with the effect of the opiate-antagonist naloxone, reversing ethanol-induced coma.

Adult↗

Endogenous opioid activity and beta-endorphin immunoreactivity in CSF of psychiatric patients and normal volunteers.

The authors measured total opioid activity by radioreceptor assay in the CSF of 41 normal subjects and 89 unmedicated psychiatric patients, including schizophrenic, schizoaffective, depressed, and manic diagnostic groups. Schizophrenic men had significantly lower levels of opioid activity than the normal men, although these levels did not significantly differ from levels of other male patients. The authors observed higher opioid activity during mania than during depression in paired samples for 4 manic-depressive patients. beta-Endorphin immunoreactivity in a subsample of the same subjects was no different in the patient group than in the normal group, suggesting that the differences in CSF opioid activity between schizophrenic men and normal patients may be related to opioids other than beta-endorphin.

Adult↗

Behavioral and biological effects of acute beta-endorphin injection in schizophrenic and depressed patients.

In this double-blind study, beta-endorphin, 4-15 mg, was administered intravenously to 6 schizophrenic and 4 depressed patients. There were neither significant differences in behavioral ratings between beta-endorphin and placebo for the overall group nor for either the schizophrenic or depressed subgroup. Clinical worsening and improvement were observed in individual schizophrenic patients. There was no evidence of late-appearing therapeutic effects in 4 schizophrenic patients rated for 5 consecutive days after placebo and drug infusions. In 1 patient 10 mg of beta-endorphin produced neuroendocrine effects comparable to those produced by 5 mg of intravenously administered methadone; in 2 other patients it produced large increases in circulating opioid activity as determined by radioreceptor assay. These biological data support the notion that parenterally administered beta-endorphin exerts significant opiate-like activity in vivo.

Adult↗

Seasonal variations in the endogenous rhythm of dopamine receptor binding in rat striatum.

In four experiments, performed at different months throughout the year, a significant daily rhythm in dopamine receptor binding has been observed. This rhythm is endogenous, as it persists in the absence of time cues. Striking differences in wave form, amplitudes, and timing of peaks during the year suggest that the endogenous rhythm undergoes seasonal variations.

Animals↗