Showing papers in "Journal of Neural Transmission in 1981"

Urinary melatonin levels in human breast cancer patients

Abstract: Urinary melatonin levels were measured in 10 postmenopausal Indian women suffering from advanced stages of breast cancer and in 9 well-matched women with non-endocrine complaints, mostly uterovaginal prolapse.

Effect of melatonin on experimental tumors under different photoperiods and times of administration

Abstract: The effects of melatonin on experimental tumors so far described in the literature are contradictory. This may partially be due to negligence of the importance of environmental photoperiodic conditions and to the time of day of administration. In order to test whether the effect of melatonin on tumor growth is dependent on the photoperiod and the time of day of administration, the present experiments were carried out. It appears that under long photoperiods melatonin shows opposite effects on fibrosarcoma ascites and Ehrlich solid tumors depending on the time of the day at which the compound was administered. Tumors are stimulated by melatonin injections in the morning and inhibited by late afternoon injections. Experiments under L∶D=12∶12 and L∶D=8∶16 do not show such pronounced antagonistic effects. These results support our hypothesis that the effect of melatonin on tumor growth is dependent on the photoperiod and the time of day of administration. Possible mechanisms involved in these effects are discussed.

Factors influencing monoamine metabolites and tryptophan in patients with alcohol dependence

Abstract: Cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and tryptophan (TRY) were measured in 36 female patients with alcohol dependence defined by strict operational criteria. Results were compared with a control group of 32 women hospitalized in a neurological unit for peripheral diseases. Several disorders presumably interfering with monoamine metabolism were carefully excluded and diet, psychomotor activity, diurnal variation, nutritional state and similar nonspecific variables controlled in both groups.

Dopamine receptors in the parkinsonian brain

Abstract: Striatal dopamine receptors were studied in 44 patients with Parkinson disease by the radioligand-binding technique using3H-spiroperidol. The specific binding of3H-spiroperidol was either significantly increased or reduced in the caudate nucleus and putamen of parkinsonian patients without levodopa therapy. Scatchard analysis showed that there were corresponding changes in the receptor number, but no significant changes in the mean dissociation constant. The increased binding of3H-spiroperidol in the basal ganglia was also found in parkinsonian patients suffering from psychotic episodes and treated with neuroleptic drugs. Normal and low binding of3H-spiroperidol was found in patients treated with levodopa. Clinically, the patients with low binding were more disabled and had lost the beneficial response to levodopa. Thus in Parkinson disease in some patients a denervation supersensitivity seemed to develop and in some others a loss of postsynaptic dopamine receptor sites in the neostriaturn. The latter alteration may contribute to the decreased response of parkinsonian patients to chronic levodopa therapy.

Distribution of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in human brain in relation to age, drug influence, agonal status and circadian variation.

Abstract: The post-mortem brain concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 16 parts of the brain from patients with no history of neurologic, psychiatric or metabolic illness. The causes of death were either ischemic heart disease, infections disease, cancer or accidents. Forty-two men with a mean age of 57 years (range 18–95 years) and 19 women with a mean age of 62 years (range 23–79 years) were included. The influence of several factors were studied: brain weight, time between death and autopsy, storage time before chemical analysis, age, sex, agonal status, cerebral arteriosclerosis, cancer, opiate treatment and time of death during the day. Most correlations between the 5-HT concentrations in different brain parts were positive, the strongest correlations in the basal ganglia and the limbic system. No consistent pattern of age-related 5-HT changes were found. The females had significantly higher 5-HIAA concentrations in the cortex of the gyrus hippocampus. Final hypoxia seemed to decrease 5-HT concentrations. Opiate treatment reduced 5-HT and increased 5-HIAA concentrations. A marked circadian variation of 5-HT was found, most pronounced in the hypothalamus, the limbic system and some neocortical areas.

Activation of striatal dopamine receptors induces pain inhibition in rats.

Abstract: In the rat, elevating dopamine content in corpus striatum with electrical stimulation of substantia nigra or direct administration of apomorphine (50–200μg) into the lateral cerebral ventricle or apomorphine (2–10μg) into the caudate-putamen complex decreased pain sensitivity (as shown by an increase in the latency to hind-paw lick in the hot plate test). Furthermore, the decreased pain sensitivity after the central administration of apomorphine was antagonized by pretreatment with haloperidol (a dopamine antagonist). On the other hand, lowering dopamine content in corpus striatum with electrolytic destruction of substantia nigra and 6-hydroxydopamine lesions to the substantia nigra, as well as direct injection of haloperidol into the lateral cerebral ventricle or caudate-putamen complex increased pain sensitivity. The data indicate that activation of striatal dopamine receptors in rat brain induces pain inhibition.

Characterization of normal and supersensitive dopamine receptors: Effects of ergot drugs and neuropeptides

Abstract: Dopamine receptors have been characterized by the use of radiolabelled dopamine agonists and antagonists. Using ibotenic acid induced lesions of the striatum, evidence was obtained that3H-N-propylnorapomorphine (3H-NPA) binding sites and3H-bromocriptine binding sites are located both on intrastriatal nerve cells and on extrinsic nerve terminals probably mainly originating in the cerebral cortex. Development of dopamine receptor super-sensitivity as evaluated in 6-hydroxydopamine lesioned rats was associated with an 50% increase in the number of3H-NPA binding sites in the striatum. Furthermore, one year following the 6-hydroxydopamine induced lesion of the dopamine pathways two binding sites for3H-NPA could be demonstrated in the striatum. However, at this time interval the total number of3H-NPA binding sites was not increased. The functional significance of these two binding sites for3H-NPA in the striatum is unknown, but they are probably coupled to the biological effector in view of the marked behavioural supersensitivity demonstrated in these old animals. The dopamine receptor agonists and especially the dopaminergic ergot derivatives have been characterized by studying their affinities for3H-bromocriptine,3H-spiperone,3H-ADTN and3H-NPA binding sitesin vitro. It is suggested that the Ki ratios for agonist and antagonist radioligands may be one useful way to characterize the agonist-antagonist character of the drug. Another important method is to study the effects of dopamine receptor agonists on the specificin vivo binding of3H-spiperone and3H-NPA. The correlation analysis of DA agonist affinities for the four radioligands of DA receptors used in the present study give evidence for the existence of at least 3 types of DA receptors. Actions of dopaminergic ergot drugs have been evaluated at supersensitive dopamine receptors. The findings suggest that the shift to the left of the threshold dose to activate supersensitive dopamine receptors could be due to a lowering of the stereoselectivity of agonist interaction at the dopamine agonist sites of supersensitive dopamine receptors. Such a change may explain the highly preferential action of CF 25-397 at supersensitive dopamine receptors, since its affinity for3H-NPA binding sites was not increased in the present experiments. In agreement with previous work, evidence have also been presented that prolonged treatment with a potent dopaminergic drug, pergolide, can produce a down regulation of normal dopamine receptors by reducing the density of such receptors. Evidence has also been presented that CCK-8 and the desulphated CCK-8 (10−6 M) canin vitro reduce the number of3H-NPA binding sites in the striatum. These results indicate that cholecystokinin peptides via activation of cholecystokinin receptors can regulate the movements of the3H-NPA binding sites across the plane of the membrane in such a way as to make them less available to the external surface of the membrane. Thus, cholecystokinin peptides and other neuropeptides may represent important neuromodulators and trophic factors in the dopamine synapses of the brain.

The sympathetic superior cervical ganglia as peripheral neuroendocrine centers.

Abstract: The superior cervical ganglia (SCG) provide sympathetic innervation to the pineal gland, cephalic blood vessels, the choroid plexus, the eye, carotid body and the salivary and thyroid glands. Removal of the ganglia brings about several neuroendocrine changes in mammals, including the disruption of water balance in pituitary stalk-sectioned rats, and the alteration of normal photoperiodic control of reproduction in hamsters, ferrets, voles, rams and goats. These effects are commonly attributed to pineal denervation. However pinealectomy does not always mimic ganglionectomy in its neuroendocrine sequelae. This paper discusses several examples illustrating the lack of homology of ganglia and pineal removal, including the prolactin release brought about by gonadal steroids in spayed rats, the changes in drinking behaviour caused by ganglionectomy and the control of goitrogenic response to methylmercaptoimidazole in rats. All these examples indicate that SCG removal, at least as far as for neuroendocrinologists and pineal experimenters are concerned, should not be considered simply as "pineal denervation". A functionally relevant link between SCG and the hypothalamus may occur in rats inasmuch as ganglionectomy depresses norepinephrine uptake and increases the number and responses of alpha-adrenoceptors in medial basal hypothalamus. Lastly the SCG are active points of concurrency for hormone signals, as revealed by the metabolic changes induced by steroid and anterior pituitary hormones in these structures even in the absence of intact preganglionic connections, as well as by the existence of putative receptors for some of the hormones, namely, estradiol, testosterone and corticosteroids. The SCG appear to constitute a peripheral neuroendocrine center.

The Effect of Catecholamine Receptor Antagonists on Ethanol-Induced Locomotor Stimulation

Abstract: The effect of various catecholamine receptor antagonists, which differ in their potency to block central dopamine and noradrenaline receptors, respectively, on ethanol-induced locomotor stimulation was investigated. It was shown that small doses of both specific dopamine (pimozide, haloperidol) and noradrenaline (phenoxybenzamine, yohimbine) receptor blocking agents statistically significantly suppressed the ethanol-induced locomotor stimulation. Of special interest in this study was the observation that remarkably small doses of clozapine completely antagonized the ethanol-induced locomotor stimulation. The possibility that this effect of clozapine is mediated via its interference with the activity of central noradrenaline and/or GABA neurons is discussed.

Influence of cholecystokinin octapeptide sulfate ester on brain monoamine metabolism in rats.

Abstract: The effects of intracerebroventricular administration of an 80 pmole dose of cholecystokinin octapeptide sulfate ester (CCK-8-SE) were tested on the dopamine (DA), norepinephrine (NE) and serotonin (5-HT) turnovers of the hypothalamus, mesencephalon, amygdala, septum, striatum and cerebral cortex in rats.

Distribution of catecholamines and serotonin in the rat cerebral cortex: absolute levels and relative proportions.

Abstract: The rat cerebral cortex was dissected in five regions and analyzed for the catecholamines noradrenaline, adrenaline and dopamine, and for the indoleamine serotonin using sensitive radioenzymatic assay methods with thin-layer-chromatography. The noradrenaline concentration was highest in the ventral cortex, lateral to the hypothalamus, had intermediate values for the prefrontal, frontal and parietal cortical areas and was lowest in the occipital cortex. Dopamine levels were also highest in the cortex lateral to the hypothalamus, and moderate in the prefrontal and frontal cortical areas, with the lowest values measured for the occipital cortex. The ratios dopamine/noradrenaline further support the hypothesis that they are independent transmitters. Traces of adrenaline were measured in all regions examined. The serotonin distribution was found to be non-homogeneous, with the highest values for the prefrontal cortex and ventral cortex lateral to the hypothalamus. The functional significance of these amines and their ratios are discussed in relation to their role as putative modulators of cortical neuronal excitability.

Chronic treatment with antidepressants: protentiation of clonidine-induced aggression in mice via noradrenergic mechanism.

Abstract: The chronic (10mg/kg i.p. twice daily, 10 days)-and not the acute-administration of amitriptyline, maprotiline or zimelidine enhances aggressiveness induced by clonidine in mice. An analogous potentiation of clonidine-induced aggressiveness was obtained with chronic administration (the schedule as above) of levomepromazine (2 mg/kg) or thioridazine (5 mg/kg) but not of spiperone (0.2 mg/kg). Fluoxetine (10 mg/kg), atropine (5 mg/kg), propranolol (10 mg/kg) or metergoline (0.5 mg/kg) given chronically (the schedule as above) also had no effect. The enhancement of clonidine aggressiveness induced by prolonged treatment with imipramine (10 mg/kg) was prevented by cycloheximide, an inhibitor of protein synthesis. The results supply further evidence for the previously proposed hypothesis that chronic administration of antidepressants enhances the responsiveness of central postsynaptic noradrenaline receptors.

Regional blockade by neuroleptic drugs of in vivo 3H-spiperone binding in the rat brain. Relation to blockade of apomorphine induced hyperactivity and stereotypies.

Abstract: The regional prevention by neuroleptic drugs of specificin vivo3H-spiperone binding was studied in the rat brain. L-sulpiride, thioridazine and clozapine were found to reduce the3H-spiperone binding selectively in the olfactory tubercle, septum, substantia nigra region and frontal cortex but not the striatum at dose levels which preferentially block apomorphine (APO) induced hyperactivity. The maximal prevention of specific3H-spiperone binding by l-sulpiride and clozapine reached 60–80% in the former structures while the displacement of striatal3H-spiperone binding did not exceed 40%. In contrast to l-sulpiride, thioridazine and clozapine both chlorpromazine and haloperidol reduced the3H-spiperone binding to the same extent in all regions studied. Chlorpromazine and haloperidol were potent in prevention of striatal3H-spiperone bindingin vivo which reached 60–80% in this structure.

Epidemiology of Parkinson's disease—An overview

Abstract: Among the white races, the prevalence rates of Parkinson's disease range from 66 to 187 per 100,000 population, through without any obvious geographical pattern. A similar variation is found in the annual incidence rates with estimates from 5 to 24 per 100,000 population. The black races may be partially protected against the disease. Both sexes are probably equally affected by the disease. Parkinson's disease usually begins after the age of 50 years, and the risk of the disease steeply rises with advancing age. Parkinson's disease is often omitted in death certificates; mortality rates with Parkinson's disease as an underlying cause of death vary from 0.5 to 3.8 per 100,000. Levodopa treatment, by reducing the excess mortality accompanying the natural course of Parkinson's disease, may increase the number of patients living with this disease in the near future. Postencephalitic Parkinson's disease, developing as a sequel to lethargic encephalitis and accounting for some two thirds of parkinsonian cases shortly after the epidemic, has probably been a transient phase in the epidemiology of Parkinson's disease and is now disappearing. Data from epidemiological investigations have advanced our understanding of the cause of Parkinson's disease only to a small extent. No other characteristic than race has been found to influence the susceptibility to the disease. The environmental risks for Parkinson's disease have not been unequivocally demonstrated. Highly conflicting information is available as to the contribution of hereditary to the pathogenesis of Parkinson's disease. Seroepidemiological investigations have shown an increased antibody response against herpes simplex virus in parkinsonian patients, but attempts to detect herpes virus specific products or DNA sequences in the brain material have been unsuccessful.

Predictors for improvement after electroconvulsive therapy in parkinsonian patients with on-off symptoms.

Abstract: The antiparkinsonian effect of electroconvulsive therapy (ECT) was investigated in nine parkinsonian patients with “on-off” phenomena. The patients were maintained on previously adjusted doses of antiparkinsonian drugs during and after ECT. Parkinsonian as well as mental symptoms were rated before and after treatment.

The sensitivity of cortical neurons to serotonin: effect of chronic treatment with antidepressants, serotonin-uptake inhibitors and monoamine-oxidase-blocking drugs.

Abstract: The sensitivity of rostral and cingulate cortical neurons to microiontophoretically administered serotonin (5-HT) was compared in groups of rats treated either acutely or chronically for different periods with various drugs. The drugs used were: desipramine (10 mg/kg), clomipramine (10 mg/kg), CGP 6085 (10 mg/kg), clorgyline (0.3 mg/kg), and deprenyl (1 mg/kg). Serotonin and, in some instances, gamma-aminobutyric acid (GABA) were applied microiontophoretically over periods of 60 sec with various ejection currents to spontaneously active neurons in the rostral and cingulate cortex. Of all the compounds tested, only clorgyline produced a marked desensitization to 5-HT in both cortical areas. After prolonged treatment with all the other drugs, no change in the sensitivity to serotonin was observed. The desensitization to 5-HT induced by clorgyline developed after 4 to 10 days of treatment. The responsiveness of these cells to GABA was unchanged after chronic exposure to clorgyline. The present results are consistent with those biochemical studies showing that chronic treatment with 5-HT-uptake-blocking compounds has no effect on 5-HT-binding characteristics, as well as with the observation that prolonged treatment with the monoamine-oxidase A-type blocker clorgyline reduces the number of 5-HT-binding sites.

3-Methoxytyramine and normetanephrine as indicators of dopamine and noradrenaline release in mouse brain in vivo.

Abstract: Intraperitoneal administration of pargyline HCl induced a dose-dependent accumulation of 3-methoxytyramine and normetanephrine in mouse brainin vivo. As judged by the decrease of 5-hydroxyindole acetic acid levels a dose of 200 mg/kg of pargyline appeared to inhibit monoamine oxidase completely. This dose led to an approximately linear accumulation of 3-methoxytyramine and normetanephrine during the first 3 hours.γ-Butyrolactone, 750 mg/kg i.p. reduced the accumulation of 3-methoxytyramine despite a marked increase of dopamine. (+)-Amphetamine stimulated 3-methoxytyramine as well as normetanephrine accumulation at doses of 3 and 10 mg/kg i.p.

Treatment of Parkinson's disease: problems with a progressing disease.

Abstract: Long-term follow-up of parkinsonian patients has shown that although levodopa treatment significantly improves the parkinsonian symptoms and the quality of life of parkinsonian patients for several years, various distressing difficulties arise during chronic levodopa treatment, such as the loss of benefit, dyskinesias, on-off phenomena, postural instability and dementia. Clinical, neuropsychological, mortality and post-mortem brain studies indicate that levodopa as a replacement therapy does not modify the progression of the underlying pathology and the natural course of the disease. It seems that levodopa has only a limited period of optimal usefulness in the treatment of Parkinson's disease. However, at present there is no better or more potent therapeutic agent available than levodopa and it is still the primary treatment of Parkinson's disease. It would be reasonable not to begin levodopa treatment in patients with mild symptoms but to withhold levodopa until the severity of symptoms really makes its use necessary. Thus it is possible to get the maximal long functional benefit. Post-mortem brain studies have shown that in Parkinson's disease there is not only a progressive loss of dopaminergic substantia nigra neurons but there are also significant changes in the striatal dopamine receptors. In some patients a denervation supersensitivity seems to develop and in some others a loss of dopamine receptors in the striatum. However, in advanced parkinsonian patients with a deteriorating response to levodopa, there seem to be still enough dopamine receptors in the striatum for drugs stimulating the dopamine receptors directly to improve the parkinsonian disability. Indeed, recent evidence indicates that dopaminergic agonists, such as bromocriptine, seem to be a significant and valuable adjuvant therapy to levodopa in parkinsonian patients with a deteriorating response and/or the on-off phenomena. Although bromocriptine is not completely satisfactory, it is a significant opening to a new mode of treatment. In the future it will be very important to develop more potent and selective dopaminergic agonists affecting only those striatal receptors which are mainly responsible for the parkinsonian symptoms. Then a better therapeutic response is likely to occur and many central side effects can be avoided. Current difficulties in the management of Parkinson's disease greatly depend on the fact that we are dealing with a symptomatic therapy. It is hoped that future research will soon lead to a discovery of the primary cause and consequently to a causal therapy of Parkinson's disease.

Neurochemical effects of some ergot derivatives: a basis for their antiparkinson actions.

Abstract: Bromocriptine and the two ergoline derivatives, CQ 32-084 and CM 29-712, excert dopamine-like effects in experimental models and have been shown to possess antiparkinsonian activity Biochemical investigations indicate that they differ in their specificity towards the different dopamine receptor types and, in addition, interact with other neurotransmitter receptors Bromocriptine appears to be a potent agonist at D2-receptors Furthermore, it blocks adenylate cyclase coupled serotonin receptors and antagonizes centralα-adrenergic receptors The two ergoline derivatives are multiple agonists CQ 32-084 stimulates both D1- and D2-, and CM 29-712 only D2-receptors In addition, both compounds stimulate adenylate cyclase coupled serotonin receptors and antagonize centralα-adrenergic receptors

Morphological and electrophysiological evidence for habenular influence on the guinea-pig pineal gland

Abstract: The central innervation of the guinea-pig pineal gland was investigated by histological and electrophysiological methods:

Effect of 5-methoxytryptophan and 5-methoxytryptamine on the reproductive system of the male golden hamster

Abstract: S.c. injections of 25μg of methoxytryptamine (5-MT) in oil into adult male hamsters given between 4.30 and 5 p.m. (light on from 5 a.m. to 7 p.m.: 14 L/10 D) for 51 consecutive days caused involution of the testes. Similar injections of 5-MT given between 8.30 and 9.30 a.m. completely failed to cause regression of the gonads. Under the same conditions, 5-methoxytryptophan (5-MTP) did not induce gonadal atrophy, neither in the morning nor in the late afternoon. These results indicate that, like melatonin, 5-methoxytryptamine is implicated in the control of the reproductive function.

Control of behaviour and brain noradrenaline neurons by peripheral blood volume receptors.

Abstract: A moderate blood volume load or experimental hemorrhage caused in the conscious rat reciprocal alterations in locomotor activity and norepinephrine turnover in brain regions largely innervated by nucleus locus coeruleus. Other brain regions as well as other central neurotransmitters (dopamine, 5-hydroxytryptamine) investigated did not show similar reciprocal changes. These data taken together with previous electro-physiological evidence support the notion that peripheral blood volume receptors participate in the control of brain norepinephrine neurons in the locus coeruleus as well as behaviour.

Individually reared rats: alteration in noradrenergic brain functions.

Abstract: The influence of social isolation in rats on postsynaptic alpha1- and beta-adrenergic receptors, on the cAMP generating system and on the presynaptic uptake mechanism in the central noradrenergic system was examined in different brain regions. Rearing rats in isolation from the 19th day of life for 12 weeks leads in all regions to a general tendency for a reduction in3H-DHA binding, to an enhanced3H-WB4101 binding and to a decreased responsiveness of the noradrenaline sensitive cAMP generating system. These changes reach significance only in the pons-medullathalamus region. Isolated rats showed an increased synaptosomal uptake of noradrenaline, most pronounced and significant in the hypothalamus. Our data provide further support for a disturbance in central noradrenergic function in isolated rats.

Regenerative synaptoneogenesis in the Mammalian spinal cord: dynamics of synaptochemical restoration in the Rolando Substance after transganglionic degenerative atrophy.

Abstract: Crush injury of the sciatic nerve, that results in Wallerian degeneration of axons in the peripheral stump, induces, within 10–14 days, transganglionic degenerative atrophy of central terminals of primary nociceptive neurons in the ipsilateral substantia gelatinosa Rolandi of the segmentally related region of the spinal cord Transganglionic degenerative atrophy is characterized by disappearance of fluoride-resistant acid phosphatase (FRAP) from the Rolando substance, normally exerted by primary nociceptive terminals From the 40th postoperative day on, FRAP reaction starts to reappear in the formerly depleted Rolando substance Restoration of FRAP reactivity reflects regenerative sprouting of formerly atrophied primary nociceptive terminals Growth cones of primary nociceptive axons establish synapses with dendritic growth cones of substantia gelatinosal cells Synaptoneogenesis in the Rolando substance follows medio-lateral and caudo-rostral gradients

Depletion in amygdaloid 5-hydroxytryptamine concentration and changes in social and aggressive behaviour.

Abstract: 5, 7-Dihydroxytryptamine (10 and 20μg) was microinjected bilaterally into the amygdaloid complex of rats and resulted in 55% and 80% depletion in 5-hydroxytryptamine concentration, respectively The lesioned animals exhibited fewer dominance behaviours and submitted more often to an intruder into their home-cages than did the vehicle-injected controls The lesioned rats were also more submissive than were the controls when they were intruding into another rat's territory Only the higher dose of toxin altered social investigatory behaviour when this was measured in an arena in which neither rat had established territory The lesioned rats displayed less social interaction and had reduced levels of motor activity The results are compared with those of other studies in which there has been regional or general depletion of brain 5-hydroxytryptamine concentration

Neuropeptides in striato-nigral pathways.

Abstract: The existence of a neuronal pathway containing Leu-enkephalin and connecting the neostriatum with the globus pallidus has been confirmed combining immunohistochemistry with microinjections of neurotoxic agents (kainic acid, colchicine) and discrete knife lesions. The presence of substance P in nerve terminals of the substantia nigra was demonstrated by the application of a monoclonal antibody against this peptide. Electron microscopic studies revealed immunoreactive sites for substance P in nerve terminals establishing symmetric and asymmetric synapses, mainly over dendritic profiles. The possible peptide-containing neuronal pathways in the nigro-striatal system are discussed.

Effects of growing tumours on pineal melatonin levels in male rats.

Abstract: The effect of transplantable tumours (Yoshida Sarcoma) on pineal melatonin content was studied in Wistar rats. A negative correlation between pineal melatonin content and size of growing tumours was observed. Effects of chronic treatment with drugs interfering with n=melatonin or serotonin biosynthesis on tumour growth as well as the influence of tumour growth on pineal melatonin content were investigated. Tumour growth enhancement observed after administration of some substances producing a decrease of pineal melatonin is discussed. Pinealectomy stimulates malignant growth. This may be caused by lack of endogenous melatonin.

Effect of sleep deprivation on dopamine receptor function in normal subjects.

Abstract: Twenty-four hours sleep deprivation significantly decreased the growth hormone response to the dopamine receptor agonist, apomorphine HCl, in five normal men (0.5 mg s.c.) and one woman (0.75 mg s.c.) but had no effect on basal or post-apomorphine prolactin concentrations. These results suggest that sleep deprivation decreases the sensitivity of certain central dopamine receptors. The relevance of this finding to the antidepressant effect of sleep deprivation is unclear.

The pineal gland of the mole (Talpa europaea L.) VII. Activity of hydroxyindole-O-methyltransferase (HIOMT) in the formation of 5-methoxytryptophan, 5-methoxytryptamine, 5-methoxyindole-3-acetic acid, 5-methoxytryptophol and melatonin in the eyes and the pineal gland

Abstract: Using a method in which no substrate is added to the incubation medium, the capacity of HIOMT to synthesize 5-methoxytryptophan, 5-methoxytryptamine, 5-methoxyindole-3-acetic acid, 5-methoxytryptophol and melatonin has been determined in the pineal and the eyes of the mole, a mammal having an atrophied visual system. The results demonstrate that the indoleamine metabolism in the retina is similar to the indoleamine metabolism in the pineal. Moreover, in all animals studied both eyes together synthesize 2 to 30 times more of 5-methoxyindoles than the pineal, a result which proves again that the pineal is not the only and not always the most important source of 5-methoxyindoles. With the exception of 5-methoxyindole-3-acetic acid, the synthesis of which is practically neglectable, the production of all other 5-methoxyindoles in the pineal as well as in the retinae is always larger than that of melatonin. In the pineal, 5-methoxytryptophan, for example, is synthesized in a quantity which is 60 to 170 times larger than that of melatonin, while in the retinae the synthesized amount of 5-methoxytryptophan is even 60 to 1000 times larger than that of melatonin.

Type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal neurons in the rat.

Abstract: Clorgyline (0.3–10mg/kg, i.p.) inhibited type A monoamine oxidase (5-hydroxytryptamine as substrate) but not type B monoamine oxidase (phenylethylamine as substrate) in homogenates of rat striatum and olfactory tubercle; deprenyl (0.3–3 mg/kg, i.p.) inhibited type B but not type A monoamine oxidase in these homogenates. The same doses of clorgyline increased concentrations of dopamine in striatum, and dopamine and norepinephrine in the olfactory tubercle, median eminence and posterior pituitary; they also reduced the concentrations of dihydroxyphenylacetic acid and the rate of synthesis of dopamine (DOPA accumulation after a decarboxylase inhibitor) in the same brain regions. On the other hand, the administration of deprenyl at doses that markedly inhibited type B monoamine oxidase did not alter the concentrations of dopamine, norepinephrine and dihydroxyphenylacetic acid or the rate of accumulation of DOPA in these brain regions. In addition, only clorgyline significantly lowered serum concentrations of prolactin. These results suggest that type A monoamine oxidase catalyzes the intraneuronal deamination of dopamine within terminals of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal dopamine neurons.