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Biomedical subjects

F K Goodwin

Publications and source records attributed to F K Goodwin.

At least 127 records · Page 7Linked to original sources
PubMed1981

Cholecystokinin receptors are decreased in basal ganglia and cerebral cortex of Huntington's disease.

Cholecystokinin (CCK) receptors were found to be significantly reduced in basal ganglia and cerebral cortex of post-mortem from Huntington's patients with matched controls. The magnitude of the reduction in CCK binding (69% in basal ganglia, 43% in cerebral cortex) is consistent with the degree of neuronal degeneration in basal ganglia, but suggests a possibly selective loss of CCK receptor-containing neurons in cerebral cortex of Huntington's patients.

Basal Ganglia↗
PubMed1981

Acceleration of beta-receptor desensitization in combined administration of antidepressants and phenoxybenzamine.

The delayed therapeutic effects of antidepressants (usually between 10 and 14 days) and of the tricyclic antidepressants in particular, are believed (on the basis of animal experiments) to lie in a progressive decrease of the sensitivity of cortical beta-adrenergic receptors. This is thought to be due to an increase in the synaptic concentration of noradrenaline, in turn accomplished by a decrease in the sensitivity of the presynaptic alpha 2 receptors which normally regulate noradrenaline secretion by a negative feedback mechanism. This model suggests that the desensitization of postsynaptic beta-receptors by antidepressants should be accelerated by the inhibition of the presynaptic alpha 2- adrenergic system, and we have indeed observed such an effect in preliminary studies with desipramine and phenoxybenzamine (PBZ) combined. We now show that the administration of either tricyclic or monoamine oxidase inhibitor antidepressants in combination with PBZ, an irreversible alpha-adrenergic blocker, accelerates and intensifies the desensitization of beta-adrenergic receptors. Our observations may have therapeutic implications.

Animals↗
PubMed1981

Interaction between purine and benzodiazepine: Inosine reverses diazepam-induced stimulation of mouse exploratory behavior.

Inosine, 2-deoxyinosine, and 2-deoxyguanosine completely reversed the increase in exploratory activity elicited in mice by diazepam. The inhibition of exploratory behavior by purines occurred at doses that when given alone have no effect on exploratory behavior. 7-Methylinosine, which does not bind to the brain benzodiazepine binding site in vitro, had no effect on the diazepam-induced increase in exploratory behavior. Behavioral effects produced by various combinations of inosine and diazepam indicate that the interaction between purine and benzodiazepine is antagonistic and support the hypothesis that the naturally occurring purines function in anxiety-related behaviors that respond to benzodiazepine treatment.

Animals↗
PubMed1981

Effects of vasopressin on human memory functions.

Arginine vasopressin and a number of its synthetic analogs augment memory functions in experimental animals. One of these analogs, 1-desamino-8-D-arginine vasopressin (DDAVP), influences human learning and memory. Cognitively unimpaired, as well as cognitively impaired adults, treated with DDAVP for a period of several days, learn information more effectively, as measured by the completeness, organization, and consistency (reliability) of recall. DDAVP also appears to reverse partially the retrograde amnesia that follows electroconvulsive treatment.

Adult↗
PubMed1981

Depressed patients have decreased binding of tritiated imipramine to platelet serotonin "transporter".

The high-affinity tritiated (3H) imipramine binding sites are functionally (and perhaps structurally) associated with the presynaptic neuronal and platelet uptake sites for serotonin. Since there is an excellent correlation between the relative potencies of a series of antidepressants in displacing 3H-imipramine from binding sites in human brain and platelet, we have examined the binding of 3H-imipramine to platelets from 14 depressed patients and 28 age- and sex-matched controls. A highly significant decrease in the number of 3H-imipramine binding sites, with no significant change in the apparent affinity constants, was observed in platelets from the depressed patients compared with the controls. These results, coupled with previous studies showing a significant decrease in the maximal uptake of serotonin in platelets from depressed patients, suggest that an inherited or acquired deficiency of the serotonin transport protein or proteins may be involved in the pathogenesis of depression.

Adult↗
PubMed1981

Age-related changes in sleep in depressed and normal subjects.

All-night electroencephalographic (EEG) sleep data were examined a function of age in normal control subjects and hospitalized, unmedicated depressed patients with primary affective illness. By analysis of variance, Total Sleep time, Delta Sleep, Sleep Efficiency, Rapid Eye Movement (REM) Sleep, and REM Latency decreased as a function of age, whereas Early Morning Awake time and Intermittent Awake time increased. Compared with normal controls, after the effects of age were covaried out, depressed patients had a greater Sleep Latency, Early Morning Awake time, Intermittent Awake time, Duration and REM Density of the first REM period, and average REM Density for the night, as well as less Sleep Efficiency, less Delta Sleep, and shorter REM Latency, Early Morning Awake time increased with age in depressives but not in normals.

Adolescent↗
PubMed1981

Methodological issues in the measurement of urinary MHPG.

UNLABELLED: Reported mean values for urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) for both depressed patients and controls vary substantially between laboratories. The present study describes methodological sources of variance affecting urinary MHPG values. Although intra-assay variance is small (coefficient of variation (CV) = 4.6%), the interassay variance is high (CV = 14.3%) and suggests caution in the interpretation of small group differences. The gas chromatographic (GC) method in this laboratory produces values highly correlated (r = 0.98) with those obtained by a reference gas chromatographic-mass spectrometric (GC-MS) method. The absolute values obtained by GC are 20% higher than those by GC-MS--a problem that may be shared to a varying extent by all GC assays. IN CONCLUSION: methodological differences do contribute to some of the variation in reported values of urinary MHPG.

Chromatography, Gas↗
PubMed1981

Cholecystokinin receptors in brain: effects of obesity, drug treatment, and lesions.

High affinity binding sites specific for cholecystokinin (CCK) and related peptides have been identified in brain. These receptors are regionally distributed, with the greatest density in the caudate nucleus and olfactory bulbs. The number of forebrain CCK receptors increases postnatally to a peak density at 12 days of age and then falls to adult concentrations by 26 days of age. Cerebral cortical (but not hypothalamic) CCK receptors were 15-18% higher (p less than 0.05) in obese rats and mice when compared with their lean littermates; however, CCK receptors were unchanged after 96 hours of fasting in normal rats. Chronic reserpine treatment (0.75 mg/kg/day X 7 days) caused a 48% increase (p less than 0.001) in the number of cerebral cortical CCK receptors, but had no effect on receptors in the caudate nucleus. Chronic d-amphetamine sulfate (5 mg/kg twice daily X 7 days) had no effect on CCK binding in cortex or caudate nucleus. Approximately 75% of the CCK receptors in the caudate nucleus are susceptible to destruction by kainic acid, indicating that they are predominantly localized to neuronal cell bodies; the remaining 25% were destroyed by severing caudal afferents to the caudate nucleus, indicating a possible presynaptic localization.

Amphetamine↗
PubMed1981

Neuropeptide modulation of social and exploratory behaviors in laboratory rodents.

Neuropeptide influences on exploratory and social behaviors were investigated, using a video-monitored computer-assisted automated animal behavior analysis system. Cholecystokinin decreased exploratory tendencies in the dose range 0.1-5.0 microgram/kg IP and 0.5-5.0 microgram/IVT, indicating a peripheral mechanism in the CCK reduction of spontaneous behaviors. Neither arginine vasopressin nor alpha-melanocyte stimulating hormone changed parameters of exploratory and social behaviors, strengthening the possibility that their roles in increasing acquisition and retention of operant tasks are specific to neural mechanisms involved in memory and learning. Analysis of spontaneous exploratory and social behavior patterns appears to be a sensitive and effective tool for detecting changes in arousal and attention to environmental stimuli which may underlie more specific behavioral effects of brain neuropeptides.

Animals↗
PubMed1981

A more sensitive radioimmunoassay for neuron-specific enolase suitable for cerebrospinal fluid determinations.

Neuron-specific enolase (NSE) and non-neuronal enolase (NNE) have been shown to be highly specific neuronal and glial products respectively and are therefore useful as biochemical markers of the two major cell types in the vertebrate central nervous system. An iodinated radioimmunoassay (RIA) procedure for human NSE (NSE-H) with approximately 50-fold greater sensitivity than the previously available tritiated assay is described. This assay is capable of detecting 100 pg of NSE-H per assay. NSE levels in human cerebrospinal fluid (CSF) which were previously undetectable with the tritiated RIA are now easily measured and have been shown to be approximately 2 ng/ml of CSF. Furthermore, results obtained with the newly described assay procedure on more concentrated brain tissue extracts are comparable to the tritiated RIA. The iodinated NSE RIA is also shown to be capable of accurately detecting added amounts of NSE in human CSF, indicating the potential clinical usefulness of this assay in determining elevated levels of NSE in CSF.

Humans↗
PubMed1981

Specific norepinephrine and serotonin uptake inhibitors in man: a crossover study with pharmacokinetic, biochemical, neuroendocrine and behavioral parameters.

Eight depressed patients with major affective illness were treated with both zimelidine, a selective serotonin-uptake inhibitor, and with desipramine, a selective norepinephrine uptake inhibitor, following a double-blind crossover design. At steady-state the active metabolite of zimelidine, norzimelidine, predominated in the CSF by a factor of 7 to 1 over parent drug. As predicted, even high concentrations of norzimelidine were not associated with decreased 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the CSF. In the same individuals, desipramine concentrations were highly correlated with decreases of MHPG in the CSF. Despite specific effects on monoamine neurotransmitter systems which have been implicated in the control of neuroendocrine secretion, neither drug had consistent effects on plasma cortisol, luteinizing hormone, growth hormone or prolactin. Both drugs had a marked and unexpected common effect on the 24-hour rest-activity cycle. The excess activity during the normal rest period (0--700 hr.) which has been noted in severely depressed individuals was significantly reduced by both the serotonergic zimelidine and the noradrenergic desipramine. These findings suggest that effects on the rest-activity pattern may be a common pathway for antidepressant effect.

Adolescent↗
PubMed1981

Urinary MHPG, stress response, personality factors and somatosensory evoked potentials in normal subjects and patients with major affective disorders.

Stressful procedures are reported to increase urinary MHPG in both normal and depressed patients. Bipolar depressed patients are also shown to be especially pain tolerant in comparison to normals. In the present study, 12 depressed patients (6 bipolar and 6 unipolar patients) and 10 normal volunteers had average evoked potentials recorded for visual and painful electrical stimuli. MHPG urinary excretion was measured during this session and during an unstimulated resting session on the home ward. Male normal volunteers showed a significant increase in urinary MHPG under stress, while no MHPG increment was noted for the depressed group. Depth of depression, assessed by the Zung and Beck scales, was found to be correlated with the reduced urinary MHPG response to stress. Possible interpretations of the results are discussed.

Adolescent↗