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Biomedical subjects

L Tamarkin

Publications and source records attributed to L Tamarkin.

At least 37 records · Page 2Linked to original sources
PubMed1987

Marked enhancement by clorgyline of nocturnal and daytime melatonin release in rhesus monkeys.

The type A monoamine oxidase (MAO)-inhibiting antidepressant clorgyline (1 mg/kg/24 days) administered to rhesus monkeys increased night-time cerebrospinal fluid (CSF) melatonin concentrations 3-fold and day-time maltonin values 5-fold. Other circadian parameters of melatonin release, including the peak time and duration of nocturnal melatonin elevation measured during continuous CSF collection periods of 90 min duration over 24-h cycles, were unaffected by clorgyline. While pinealocytes are thought to contain only MAO-B, treatment with the selective MAO-B inhibitor deprenyl (2 mg/kg/24 days) did not alter day or night-time melatonin concentrations. These results are consistent with MAO-A and non-selective MAO inhibitors acting via blockade of degradation of the preferential substrates of MAO-A, serotonin and/or norepinephrine, in adrenergic neurons entering the pineal gland. Further study is needed to evaluate the relative contributions of an increased availability of the melatonin precursor, serotonin, or a sustained net increase in alpha 1-or beta adrenoceptor-mediated input on pinealocytes to these marked changes in melatonin production.

Animals↗
PubMed1987

Differential response of rat splenic lymphocytes to short-term and long-term neuroendocrine challenges: possible desensitization of the cellular immune response to corticosteroids.

The effects of acute or chronic in vivo or in vitro exposures to supra-physiologic doses of isoproterenol, insulin or dexamethasone on rat splenic lymphocyte proliferation were investigated. Acutely, all in vivo challenges inhibited mitogen-induced lymphocyte proliferation, and correlated to increased corticosterone levels. However, chronic in vivo exposure to dexamethasone resulted in lymphocyte activity which was equivalent to controls, while chronic isoproterenol treatment enhanced the lymphocyte response to mitogen. These data suggest that chronic stress may result in a desensitization of the immune system to corticosteroids as well as a direct in vivo modulation by isoproterenol to enhance lymphocyte proliferation.

Adrenalectomy↗
PubMed1987

Treatment of a patient with seasonal premenstrual syndrome.

The authors identified a patient who had premenstrual syndrome (late luteal phase dysphoric disorder) only in the fall and winter and was virtually asymptomatic during the spring and summer. On the basis of previous experience with seasonal affective disorder, they treated the patient with bright artificial light, which reversed her symptoms. On subsequent occasions they reversed this treatment effect with oral melatonin administration and found that propranolol and atenolol, beta-antagonists that inhibit the production of melatonin, had a therapeutic effect similar to that of light. They discuss the implications of these findings in relation to the importance of melatonin as a mediator of seasonal rhythms in biology.

Adult↗
PubMed1987

Sex-differences in ethanol sensitivity and alcohol and aldehyde dehydrogenase activities in the Syrian hamster.

Because male Syrian hamsters demonstrate greater preference for ethanol than female hamsters, we compared them with regard to ethanol sensitivity and hepatic alcohol and aldehyde dehydrogenase activities. Male hamsters were slower to recover righting response and had lower blood alcohol levels upon recovery than did females. Hepatic alcohol dehydrogenase activity was approximately twice as high in females as males, but gender differences were not found for either cytosolic or non-cytosolic aldehyde dehydrogenase activities. The results suggest that the reduced ethanol sensitivity of female hamsters is due to more rapid metabolism. However, the finding that female hamsters have higher blood alcohol concentrations upon recovery also suggests the possibility of reduced CNS sensitivity.

Alcohol Dehydrogenase↗
PubMed1986

Pineal function during ethanol intoxication, dependence, and withdrawal.

Pineal melatonin and serotonin content were determined during one to four days of continuous intoxication, and during the alcohol withdrawal syndrome. The nocturnal rise in pineal melatonin was blunted in continuously intoxicated animals, however this was found to be unrelated to duration of treatment. The initial dependent-intoxicated phase of the alcohol withdrawal syndrome produced a reduction of nocturnal pineal melatonin content with a concomitant elevation in pineal serotonin. The overt withdrawal phase of the alcohol withdrawal syndrome had no effect on pineal melatonin or serotonin content. This data suggests that ethanol may perturb pineal melatonin synthesis either directly, or indirectly by altered receptor function. Contrary to our expectations the pineal may not be a useful model to probe the physiology of increased noradrenergic neurotransmission produced by ethanol withdrawal.

Alcohol Withdrawal Delirium↗
PubMed1986

Phototherapy of seasonal affective disorder. Time of day and suppression of melatonin are not critical for antidepressant effects.

Seasonal affective disorder is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). In winter, depressed patients with seasonal affective disorder respond to daily treatments with five to six hours of bright artificial light in two to three days. They relapse two to three days after light is withdrawn. In this study carefully controlled experimental conditions were used to determine whether phototherapy acts via a photoperiodic mechanism in which the timing of light is critical for its therapeutic effect. Photoperiodism is a common regulatory mechanism in animal seasonal rhythms and depends for its effect on light-induced changes in the pattern of nocturnal melatonin secretion. The results reported herein of "skeleton photoperiod" experiments indicate that the efficacy of phototherapy may not depend on its timing or its effect on melatonin secretion.

Circadian Rhythm↗
PubMed1986

Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranylcypromine but not deprenyl.

Melatonin was measured in plasma collected between 8:00 and 8:30 a.m. from 27 depressed patients studied before and after 21- to 24-day treatment with three monoamine oxidase (MAO) inhibitors. Baseline plasma melatonin concentrations determined by radioimmunoassay were 4.0 +/- SD 4.7 pg/ml. Tranylcypromine, a nonselective MAO inhibitor given in doses of 20-40 mg/day for 3 weeks, significantly elevated plasma melatonin to 10.6 +/- SD 2.0 pg/ml. Clorgyline, given in doses of 15-30 mg/day for 3 weeks, produced a significant, approximately three-fold increase in plasma melatonin (13.6 +/- SD 13.5 pg/ml). This clorgyline dose was selective for MAO type A inhibition, as MAO-B activity measured in platelets from the same blood samples was unaffected by clorgyline. In contrast, the selective MAO-B inhibitor deprenyl (10-30 mg/day for 3 weeks) led to a 96 +/- 4% inhibition of platelet MAO-B activity but no significant change in plasma melatonin (5.1 +/- SD 4.2 pg/ml). As both serotonin and norepinephrine are preferentially metabolized by MAO-A rather than MAO-B, an increased availability of serotonin (the precursor of melatonin) or enhanced noradrenergic function might mediate the melatonin changes observed to follow MAO-A but not MAO-B inhibition.

Blood Platelets↗
PubMed1986

Circadian timekeeping in narcoleptic dogs.

Anatomical and functional aspects of the circadian timekeeping system containing the suprachiasmatic nucleus (SCN) were compared in normal and genetically narcoleptic dogs. The retinohypothalamic tract was delineated by tritiated amino acid autoradiography, the SCN was identified and examined by morphological techniques, and the circadian rhythm of melatonin concentrations in cerebrospinal fluid was measured by radioimmunoassay. Results suggest that the retinal input, cytoarchitecture, and essential timekeeping function of the SCN are intact in narcoleptic dogs.

Animals↗
PubMed1986

Pineal melatonin rhythms in female Turkish hamsters: effects of photoperiod and hibernation.

Daily rhythms of pineal and serum melatonin content were characterized for adult female Turkish hamsters (Mesocricetus brandti) exposed to long days (16L:8D, 22 degrees C) or after transfer to short days (10L:14D, 22 degrees C). The nocturnal peak of pineal melatonin content was found to be approximately 3 b greater in duration on short than on long days. Changes in levels of serum melatonin closely paralleled those of pineal melatonin. Thus, an effect of photoperiod on synthesis and secretion of pineal melatonin was demonstrated. In a separate experiment, female hamsters were induced to hibernate by exposure to a short-day, cold environment (10L:14D, 6 degrees C). During the 4 to 5-mo hibernation season, Turkish hamsters are known to display 4 to 8-day hours of torpor (body temperature = 7-9 degrees C) alternating with 1 to 3-day intervals of euthermia (body temperature = 35-37 degrees C). Little evidence of nocturnal synthesis or secretion of pineal melatonin was detected in females sampled during torpor. However, animals sampled during the first day after arousal from a torpor bout displayed melatonin rhythms no different in phase or amplitude from those seen in females held at 22 degrees C. Thus, despite the absence of pineal melatonin output during torpor, the pineal gland of hibernating Turkish hamsters produces an appropriately phased, rhythmic melatonin signal during intervals of euthermia.

Aging↗
PubMed1986

Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function.

Antidepressants and some other psychotropic drugs affect the synthesis and release of melatonin through several mechanisms. Monoamine oxidase (MAO)-inhibiting antidepressants increase pineal concentrations of the melatonin precursors, serotonin (5-HT) and N-acetyl serotonin (NAS), in rodents, and also increase pineal N-acetyl transferase activity as well as both daytime and nighttime plasma melatonin concentrations; they also elevate melatonin, 5-HT and NAS in the cerebrospinal fluid of non-human primates. In humans treated with the MAO-A selective inhibitor, clorgyline, or the nonselective inhibitor, tranylcypromine, increased plasma melatonin also occurs; in contrast, the MAO-B selective inhibitor, 1-deprenyl, does not affect plasma melatonin. Chronically-administered tricyclic antidepressants with prominent effects on monoamine uptake and on beta-adrenoceptors reduce pineal and plasma melatonin in rodents; however, in two studies in depressed patients, either no change or a significant elevation in nocturnal plasma melatonin followed 3 to 4 weeks treatment with desipramine. As depressed patients in these and several other recent studies had lower pretreatment nighttime melatonin peaks than controls, these findings may be relevant to the presynaptic and receptor adaptational consequences of chronic antidepressant drug treatment. The significant effects on melatonin of other drugs which affect monoamine function and have psychotropic effects, including lithium, propranolol, amphetamine and several monoamine precursors, together with recent observations of the existence of muscarinic and benzodiazepine receptors in the pineal gland are in accord with previous suggestions that the study of pineal function and melatonin production provides a valuable model system for psychopharmacological investigations.

Animals↗
PubMed1986

Melatonin in seasonal affective disorder and phototherapy.

In several studies we have found that treatment with bright environmental light, capable of suppressing human melatonin, reverses the winter depressive symptoms of patients with seasonal affective disorder (SAD), whereas light too dim to suppress human melatonin is therapeutically ineffective. This finding, as well as the central importance of melatonin as a hormonal mediator of photoperiodic changes on seasonal rhythms in animals, led us to test the hypothesis that melatonin mediates the effects of shortening days on the winter symptoms of SAD and that the modification of melatonin secretion by bright light mediates its antidepressant effects. We partially reversed the antidepressant effects of phototherapy in 8 SAD patients by oral melatonin administration, but in another study of 19 SAD patients we failed to find any therapeutic difference between the beta-adrenergic blocker, atenolol, which inhibits melatonin secretion, and placebo. In a third study of 7 SAD patients we showed that the anti-depressant effects of phototherapy were not photoperiodic and appeared to be independent of melatonin suppression. There is some preliminary evidence that melatonin secretion may be abnormal in SAD. We conclude that while melatonin may play some role in the symptoms of SAD and the effects of phototherapy, it cannot by itself account for these phenomena.

Animals↗
PubMed1985

Maturation of the pineal melatonin rhythm in long- and short-day reared Djungarian hamsters.

Male Djungarian hamsters, reared under long (16L/8D) or short (10L/14D) days, were sacrificed at various ages during the day or night, or at night following a 30-min light pulse. The pineal melatonin rhythm matured similarly under long and short days by 20 days of age. The results are discussed in context of the hypothesis that melatonin mediates the photoperiod effects which forestall puberty in short-day reared hamsters.

Animals↗
PubMed1985

Melatonin: a coordinating signal for mammalian reproduction?

There is a daily rhythm in the production of the pineal hormone melatonin in all mammalian species. Production is stimulated by darkness and inhibited by light. This provides a signal reflecting the changing environmental lighting cycle. In seasonally breeding mammals that use changes in the photoperiod to time their reproductive cycles, temporal signals to the reproductive system are controlled by the daily rhythm in melatonin production.

Animals↗
PubMed1985

Melatonin and malignant disease.

A possible role for the pineal and melatonin in malignant disease is suggested by the studies of hormone-dependent tumours presented here. The most dramatic observation of the effect of the pineal and melatonin in malignancy is that melatonin protects against, while pinealectomy enhances, 7,12-dimethylbenz[a]anthracene-induced mammary tumours in rats. Melatonin may protect against tumours through a suppressive effect on prolactin secretion or an action on oestrogen receptors. Melatonin can change the concentration of oestrogen receptors in hamsters, both juvenile and adults, and in a human breast cancer cell line. The long-term effect of melatonin in the ovariectomized adult hamster and in human breast cancer cells is to inhibit oestrogen-stimulated growth. A possible relationship between melatonin and oestrogen receptors was examined in women with breast cancer. An inverse correlation was observed between the oestrogen receptor concentration in each patient's tumour and her peak plasma melatonin level, suggesting that the more hormone dependent the breast cancer the more blunted the daily melatonin rhythm. Thus, the more robust the daily melatonin rhythm the greater the protective effect on hormone-dependent breast cancer. Unfortunately, this hypothesis is not easily tested as shown in a study of women at high risk for developing breast cancer. These women had daily melatonin profiles that did not differ from those of a normal population. Thus, the use of plasma melatonin as a screening tool for breast cancer risk is not reasonable; however the basic and clinical data argue that the role of melatonin in endocrine-related cancers requires more extensive clinical investigation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Serum melatonin and pineal indoleamine metabolism in a species with a small day/night N-acetyltransferase rhythm.

Ovine serum and pineal melatonin levels are low during the day, increase five to ten-fold at night, decrease during a light pulse at night, and rapidly increase to night levels following the light-dark transition. N-Acetyltransferase activity increases three-fold at night, falls significantly in response to the light pulse, but does not increase following the light pulse. No significant change in N-acetylserotonin occurs under these conditions. These results suggest that the biochemical mechanisms controlling pineal melatonin synthesis in the sheep pineal gland may be different from those in the rat.

Acetyltransferases↗