Showing papers in "Journal of Neural Transmission in 1980"
TL;DR: Cross-correlation studies of the data indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain, consistent with a genetic regulation of the enzyme forms.
Abstract: The effect of age upon monoamine oxidase -A and -B (MAO-A and -B) in 23 different regions of human brain was determined. There was a significant positive correlation with age in 19 out of 23 regions for MAO-B, but no positive correlation with age was found for MAO-A. The increased MAO-B activity was found, in 5 out of 5 regions tested, to be due entirely to an increased enzyme concentration, rather than due to an increased molecular turnover number of the enzyme. The responses of the mitochondrial marker enzymes succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were studied in 5 brain regions, and no consistent change in activity found with age. The lysosomal enzyme acid phosphatase was found to tend towards an increased activity with age. No difference in either the specific activities or molecular characteristics of MAO were found between men and women. Cross-correlation studies of the data, after compensation for the effects of age, indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain. Such a finding is consistent with a genetic regulation of the enzyme forms.
326 citations
TL;DR: The day and night rhythms in the activity of HIOMT in the formation of melatonin and of 5-methoxytryptophol have been determined in the pineal, retina and Harderian gland of the adult male golden hamster.
Abstract: The day and night rhythms in the activity of HIOMT in the formation of melatonin and of 5-methoxytryptophol have been determined in the pineal, retina and Harderian gland of the adult male golden hamster. In all hamsters used there was no detectable HIOMT activity in the deep pineal. In the superficial pineal HIOMT activity, involved in the synthesis of melatonin (Mel), was observed to be high at the end of the dark period and at the middle of the light period. Considering the HIOMT activity involved in the production of 5-methoxytryptophol (5-MTL), an increase in 5-MTL synthesis was observed only during the light period. Comparing the peak of Mel-production with that of 5-MTL it appears that during the light period the pineal produces more 5-MTL than Mel. In the Harderian glands, the circadian course of HIOMT activity involved in the synthesis of Mel seems to run parallel to that of the enzyme implicated in 5-MTL synthesis, both being stimulated at the end of the dark period. The activity of HIOMT in 5-MTL production is, however, always approximately 2 times higher than for Mel synthesis. In the retina the synthesis of Mel and 5-MTL is not significantly higher during the dark period than during the light period. However, the production of 5-MTL is larger than that of Mel. It appears that (1) with the exception of the end of the dark period, the extra-pineal synthesis of Mel and 5-MTL is always higher than that in the pineal; (2) the circadian synthesis of 5-methoxyindoles is different in each organ, and (3) in the pineal the circadian activity of HIOMT involved in 5-MTL formation is different from that of the same enzyme involved in the formation of Mel. The results are discussed.
113 citations
TL;DR: The results suggest that the stimulation of noradrenaline neurons in the LC by cholinergic drugs such as physostigmine is mediated via cholinerential, muscarinic receptors within this nucleus.
Abstract: The significance of the cholinergic receptors within the noradrenergic nucleus locus coeruleus (LC) was analyzed by using single unit recording techniques and microiontophoretic drug application of various cholinergic and anticholinergic drugs. Physostigmine (25--50 micrograms/kg), intravenously administered, caused increased firing of LC neurons and this effect was blocked by scopolamine but not by methylscopolamine. Also nicotine (10--50 micrograms/kg i.v.) caused activation of LC neurons, an effect which was antagonized by the presumed nicotinic antagonist mecamylamine (8 mg/kg) as well as scopolamine (0.5 mg/kg i.v.). The cholinergic receptor within the LC showed specific muscarinic characteristics since microiontophoretic application of various muscarinic agonists caused excitation of LC units, whereas microiontophoretically applied nicotine had no effect. In addition, the acetylcholine (ACh)-induced excitation of the LC neurons was not blocked by nicotinic antagonists but was totally antagonized by the muscarinic agonist scopolamine. Scopolamine, when microiontophoretically applied onto the LC neurons, antagonized the stimulatory effect of systemically injected physostigmine but not that of nicotine. These results suggest that the stimulation of noradrenaline (NA) neurons in the LC by cholinergic drugs such as physostigmine is mediated via cholinergic, muscarinic receptors within this nucleus. The LC activation by nicotine is, however, an indirect effect, probably involving central ACh release and mediated via a non-cholinergic LC input.
98 citations
TL;DR: Results indicate that neuro-hormonal balances, implicated in pineal-hypothalamo-pituitary hormonal regulation, play a role in tumor induction and tumor growth of mammary tumors in female rats, probably by modifying peripheral hormone secretion.
Abstract: Stress modifies the neurohormonal balance of biogenic amines (catecholamines and indoleamines such as serotonin and melatonin). An experimental approach for investigation of the possible role of such neurohormonal balances on tumor induction and tumor growth can be achieved by administration of melatonin, by pinealectomy or by varying the nycthemeral cycle of lighting. In the case of mammary tumors induced in female Sprague-Dawley rats by per os administration of 7.12 DMBA, two important observations were made: the carcinogenic compound alters the levels of pituitary serotonin, particularly at the level of the intermediary lobe, and melatonin seems to play a role in restricting tumor development.
92 citations
TL;DR: The antiparkinsonian effect of ECT is probably mediated by increased sensitivity in postsynaptic DA structures, and may be useful as a supplementary treatment in parkinsonian patients with “on-off” phenomenon.
Abstract: During long-term treatment with L-dopa in Parkinson's syndrome “on-off” phenomenon develops in many cases, often entailing considerable therapeutic problems. Decreased sensitivity in postsynaptic striatal dopamine (DA) receptors has been shown to occur in parkinsonian patients during long-term treatment with L-dopa. This has been suggested as one possible mechanism for development of the “on-off” phenomenon. In contrast to L-dopa treatment electroconvulsions have been shown to increase sensitivity in the DA receptors, when administered to animals. The antiparkinsonian effect of electroconvulsive therapy (ECT) was investigated in five parkinsonian patients with “on-off” phenomenon, with or without concomitant signs of mental depression. ECT was administered according to praxis in treatment of mental depression. Drug therapy, including L-dopa, was maintained on previously adjusted doses during and after ECT. A marked improvement in the parkinsonian symptoms as well as in the “on-off” phenomenon occurred in three of the patients, persisting for several months. The other two patients showed only slight and transient improvement. It thus seems that ECT may be useful as a supplementary treatment in parkinsonian patients with “on-off” phenomenon. The antiparkinsonian effect of ECT is probably mediated by increased sensitivity in postsynaptic DA structures.
91 citations
TL;DR: It was revealed that morphine increases the activity of nigrostriatal and mesolimbic DA nerves which terminate in the striatum, nucleus accumbens and olfactory tubercle, but reduce the activity in the median eminence, while Naloxone blocked the effects of morphine on DOPA accumulation.
Abstract: On the basis of biochemical indices of dopamine (DA) nerve activity (decline of DA after inhibition of tyrosine hydroxylase, accumulation of DOPA after inhibition of DOPA decarboxylase) it was revealed that morphine increases the activity of nigrostriatal and mesolimbic DA nerves which terminate in the striatum, nucleus accumbens and olfactory tubercle, but reduce the activity of tuberoinfundibular DA nerves which terminate in the median eminence. Morphine had no effect on tuberohypophyseal DA nerves which project to the posterior pituitary. Naloxone was without effectper se, but blocked the effects of morphine on DOPA accumulation. Thus, morphine differentially alters the diverse DA neuronal systems in the rat brain.
80 citations
TL;DR: Findings show test-specific effects after enhancement of central 5-HT neurotransmission and it is suggested that various aspects of pain sensitivity and morphine analgesia may involve different 5- HT pathways in the brain and spinal cord.
Abstract: The effects of the specific 5-HT uptake inhibitors alaproclate and zimelidine, the 5-HT releasing compound p-chloroamphetamine (PCA) and the specific NA uptake inhibitor desipramine on pain sensitivity were examined in male rats using the hot-plate and tail-flick methods. The effects of alaproclate and zimelidine on 5-HT uptake mechanisms in the hypothalamus and spinal cord were also studied. Alaproclate, zimelidine, PCA and desipramine produced hypoalgesia in the hot-plate but not in the tail-flick test. Naloxone (1 mg/kg) failed to block the hypoalgesia produced by alaproclate and PCA in the hot-plate test. Zimelidine but not desipramine pretreatment blocked the analgetic action of PCA in the hot-plate test. Alaproclate significantly enhanced morphine analgesia in the hot-plate test but did not affect morphine analgesia in the tail-flick test. In contrast, zimelidine tended to enhance and significantly prolonged morphine analgesia in the tail-flick test but did not affect morphine analgesia in the hot-plate test. Zimelidine inhibited 5-HT uptake with equal potency in the hypothalamus and spinal cord, while alaproclate produced a greater inhibition of 5-HT uptake in the hypothalamus. These findings show test-specific effects after enhancement of central 5-HT neurotransmission. It is suggested that various aspects of pain sensitivity and morphine analgesia may involve different 5-HT pathways in the brain and spinal cord. Moreover, 5-HT pathways in the forebrain may mediate analgesia of a non-opiate type.
74 citations
TL;DR: Findings do not support a major role for the serotoninergic system on basal anterior pituitary hormone secretion in man, possibly with the exception of the ACTH-cortisol secretion.
Abstract: The endocrinological actions of quipazine, a direct serotonin receptor agonist, were investigated in both normal subjects (NS) and individuals with neurological disorders,i.e., Huntington's disease (HD), myoclonic epilepsy (ME) and cluster headache (CH). In both normal subjects and neurologic patients inconsistent and variable changes in the secretion of anterior pituitary hormones were observed. In fact, oral administration of 50 mg of quipazine elicited a rise in plasma GH in only 9/23 subjects investigated (3 NS, 2 HD, 1 ME, 3 CH), decreased GH in 4 subjects (1 NS, 2 HD, 1 CH) and left unmodified plasma GH in the remaining 10 subjects. Only 7/23 subjects showed a positive PRL response to quipazine (2 NS, 1 HD, 1 ME, 3 CH), in one subject (CH) PRL was inhibited while the drug was ineffective in the remaining 15 subjects. For gonadotropins, 5/21 subjects (2 NS, 1 HD, 2 CH) had a positive LH response and 3/20 subjects (1 NS, 1 ME, 1 CH) had a positive FSH response. In one subject (HD) there was inhibition of baseline LH levels and no effects were present in the remaining individuals. No changes in basal TSH levels were present in the 6 subjects investigated (4 NS, 2 ME). Quipazine was instead competent to increase plasma cortisol levels in 6/8 normal subjects. Pharmacodynamic, mainly gastrointestinal, effects of the drug were present in about 50% of the subjects but were not or only poorly correlated with the endocrine responses. Collectively, based on the neuropharmacologic profile of the drug, and in contrast to many animal data, these findings do not support a major role for the serotoninergic system on basal anterior pituitary hormone secretion in man, possibly with the exception of the ACTH-cortisol secretion.
52 citations
TL;DR: Results indicate that several LC neurons have both contralateral and bilateral projections to the brain areas mentioned above.
Abstract: Evans Blue (EB) and a mixture of 4′-6-diamidino-2-phenylindol 2 HCl and primuline (DAPI-Pr), fluorescing at different wave-lengths were injected into the rat hippocampus, frontal cortex or lateral part of the thalamus. After unilateral injection either of the two substances was retrogradely transported not only to ipsilateral but also to contralateral locus coeruleus (LC) neurons. Moreover after simultaneous injections of EB and DAPI-Pr respectively into the opposite brain structures of individual animals double-labeled neurons were observed in the bilateral LC.
50 citations
TL;DR: Long-term electrophysiological recordings from the guinea-pig pineal organ show that three types of intrinsic cells can be distinguished: light- and darkness-activated cells which closely follow season-dependent differences in day- and night-lengths.
Abstract: Long-term electrophysiological recordings from the guinea-pig pineal organ show that three types of intrinsic cells can be distinguished: (i) Cells showing constant firing rates over periods of up to 24 hours. (ii) Cells which are highly active during the day and show a low firing rate during the night. (iii) Cells which exhibit low activity during the day and enhanced activity during the night; these cells can be strongly inhibited by 1 min of light given during the night. Both the light- and darkness-activated cells show activity patterns which closely follow season-dependent differences in day- and night-lengths. In addition, both cell types show an oscillatory pattern in maintained activity.
47 citations
TL;DR: It is concluded that, besides the generally accepted regulation of the indole metabolism by light, in species with atrophied eyes having Harderian glands (mole rat) and in species without eyes other factors than light might be responsible for the indoles metabolism in the pineal gland.
Abstract: Hydroxyindole-O-methyltransferase (HIOMT) activity for the synthesis of melatonin and 5-methoxytryptophol, both 5-methoxyindoles, was measured in the pineal, the Harderian gland and the retina of the mole rat and in the pineal of the mouse “eyeless”. In the pineal and the Harderian gland of the mole rat a larger amount of 5-methoxytryptophol than of melatonin is synthesized. 5-Methoxyindole synthesis is extremely high in the Harderian gland, whereas in the retina HIOMT activity is low and variable. In the pineal of the mouse “eyeless”, a low 5-methoxyindole synthesis showing no circadian rhythm is demonstrated. It is concluded that, besides the generally accepted regulation of the indole metabolism by light, in species with atrophied eyes having Harderian glands (mole rat) and in species without eyes other factors than light might be responsible for the indole metabolism in the pineal gland.
TL;DR: The results are compatible with the notion that the depression of exploratory behaviour by clonidine is related to impaired central NA-neurotransmission and rule out the possibility that it is due to activation of central post-synaptic NA-(α-)receptors.
Abstract: Administration of clonidine, 0.05 mg/kg i.p. to mice 30 min before trial significantly depressed the exploration of a Y-maze. This effect was completely antagonized by 1-amphetamine, 0.75 mg/kg i.p., given 10 min before trial, which by itself did not change the behaviour studied. The clonidine-induced behavioural depression also appeared reduced after pretreatment with desipramine (10 mg/kg i.p., 30 min before clonidine) which, like l-amphetamine, by itself was inactive. The above treatment with clonidine significantly reduced the accumulation of dopa after inhibition of central aromatic L-amino acid decarboxylase both in the noradrenaline (NA) rich neocortex and the dopamine-rich neocortex and the dopamine-rich corpus striatum, whereas the dopa accumulation in the limbic brain regions was not significantly affected. l-Amphetamine, 0.75 mg/kg i.p., did not by itself significantly affect the dopa accumulation, but reduced the clonidine-induced effects. The results are compatible with the notion that the depression of exploratory behaviour by clonidine is related to impaired central NA-neurotransmission and rule out the possibility that it is due to activation of central post-synaptic NA-(alpha-)-receptors.
TL;DR: In mice with well established mammary tumors, prolactin or estrogen have relatively little effect since these tumors are largely autonomous, and in women there is inconclusive evidence as yet that prolact in plays a role in breast cancer development and growth.
Abstract: The regulation of hormonal influences on mammary tumor development and growth resides in the hypothalamus. The two major hormones essential for mammary tumor development in the rat and mouse, and also for mammary tumor growth in the rat, are prolactin and estrogen. Prolactin secretion is directly controlled by the hypothalamus, and estrogen indirectly via the pituitary gonadotropins. Treatments that increase prolactin secretion in the rat and mouse increase the incidence of spontaneous mammary tumors, whereas treatments that decrease prolactin or estrogen secretion decrease the incidence of spontaneous mammary tumors in these species. In carcinogen treated rats, either an increase or decrease in prolactin or ovarian hormones inhibits development of mammary cancers.
TL;DR: In this paper, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine(a selective 5HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses.
Abstract: In a double-blind placebo-controlled study, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine (a selective 5-HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses. Ten normal volunteers received randomized and in weekly intervals oral single doses 50 mg, 75 mg and 125 mg clovoxamine, 75 mg fluvoxamine, placebo and as reference drug 75 mg imipramine. Quantitative EEG, psychometric data, pulse, blood pressure, side effects and pharmacokinetic data were studied at the hours 0, 2, 4, 6 and 8. Plasma levels of both substances peaked in the 4th to 6th hour and declined slowly thereafter. Digital computer period analysis of the EEG demonstrated after clovoxamine only minor changes characterized by an increase of fast beta-activities suggesting slight activating qualities of the drug. On the other hand 75 mg fluvoxamine and especially 75 mg imipramine produced marked CNS changes characterized by a concomitant increase of slow and fast activities and a decrease of alpha-activity. However, 75 mg fluvoxamine induced less augmentation of slow activity than imipramine indicating less sedative properties of fluvoxamine than the standard reference drug. Psychometric tests demonstrated after 50 and 75 mg clovoxamine and 75 mg fluvoxamine an increase in attention, attention variability, concentration, CFF and after-effect in the Archimedean Spiral (indicating central activation), further an improvement in mood and affectivity as compared with placebo, while 125 mg clovoxamine and 75 mg imipramine produced an increase in reaction time, deterioration of mood and affect and psychomotor activity. The latter changes were observed also after other antidepressants in normals. Pharmacodynamic investigations regarding dose-efficacy and time-efficacy relations based on both EEG and psychometric parameters revealed that 75 mg imipramine was the most effective compound, followed by 75 mg fluvoxamine and 125 mg, 75 mg and 50 mg clovoxamine. The peak effect of clovoxamine and fluvoxamine was observed around the 6th hour, while 75 mg imipramine was maximally effective between the 2nd and the 4th hours. Side effects were minimal after clovoxamine (interestingly euphoria in 3 subjects), while tiredness was seen in 5 out of 10 subjects after 75 mg fluvoxamine and in 8 out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.
TL;DR: The results from this investigation clearly indicate that the maturation of the different biochemical parameters of the 5-HT pathways develop in a caudal to rostral direction and supports the view that tryptophan hydroxylase may be the limiting step in the development of the serotoninergic system.
Abstract: Various characteristics of the developing serotoninergic system in the brain of rats aged 1 to 28 days were studied biochemically. The levels of the precursor amino acid tryptophan showed a maximal increase in the blood, brain and cerebrospinal fluid (CSF) during the 7th and 10th postnatal days. The development of tryptophan hydroxylase activity measuredin vivo by means of 5-hydroxytryptophan (5-HTP) accumulation after NSD 1015 was closely related to the 5-hydroxytryptamine (5-HT) levels at the various ages. 5-HTP accumulation and 5-HT levels increased most markedly after the second postnatal week. 5-Hydroxyindoleacetic acid (5-HIAA) levels were found to increase rapidly in the brain but somewhat more slowly in the CSF during the second week of postnatal development. Regional studies of 5-HTP accumulation after NSD 1015, 5-HT and 5-HIAA levels indicated a caudal to rostral way of maturation. The disappearance of 5-HT was measured after inhibition of tryptophan hydroxylase with H 22/54. The half-life generally decreased in the various brain parts with advancing age, and in the younger animals the shortest half-life was found in the most caudal brain parts. At 28 days of age the half-life was similar in all brain parts studied. These results indicate the existence of an adult like nerve impulse flow in the 5-HT neurons in the brain stem region of the newborn rats. The results from this investigation clearly indicate that the maturation of the different biochemical parameters of the 5-HT pathways develop in a caudal to rostral direction. The study also supports the view that tryptophan hydroxylase may be the limiting step in the development of the serotoninergic system.
TL;DR: The cholinergic innervation of the dura mater in the guinea pig, mouse and rat has been investigated and acetylcholinesterase (AChE)-containing nerve fibers in close relationship with the main meningeal blood vessels are found.
Abstract: The cholinergic innervation of the dura mater in the guinea pig, mouse and rat has been investigated. The dura mater is provided with a cholinergic innervation. After short incubation times (4--6 hours) we found acetylcholinesterase (AChE)-containing nerve fibers in close relationship with the main meningeal blood vessels. After longer incubation times, AChE-containing nerve fibers appear also in the meningeal tissue proper. Chemical sympathectomy, performed with the neurotoxin 6-hydroxy-dopamine, does not seem to interfere with the pattern of the dural cholinergic innervation. The findings are discussed.
TL;DR: The results obtained point to the secretion of androgens and the insufficiency of the antiandrogenic function of the pineal gland both in auditory stress and ulcer disease.
Abstract: A short survey of the results of our previous research into the protective role of the pineal gland against stress is given. The neuroendocrine aspect of a chronic auditory stress and the neuroendocrine aspect of ulcer disease in man were studied. Auditory stress: hypertrophy and hyperplasia of pinealocytes, hyperplasia of the STH, FSH, LTH and TSH cells, hypertrophy of the nuclei and nucleoli of the neuroglandular cells of the supraoptic and paraventricular nuclei, pronounced hyperplasia of the cells of the reticular zone of the adrenal gland, involution of the seminal epithelium, hyperplasia of the Leydig cells. Ulcer disease: numerous glial plates, cavities and acervuli in the pineal gland, numerous granules and vacuoles in the FSH cells, large and eccentrical nuclei in the LH cells, hyperplasia of the cells of the reticular zone of the adrenal gland, presence of the seminal tubules marked by signs of involution, hyperplasia of the Leydig cells. The results obtained point to the secretion of androgens and the insufficiency of the antiandrogenic function of the pineal gland both in auditory stress and ulcer disease. The anticancerogenic effect of the pineal gland would be based on its antiandrogenic function.
TL;DR: In animals pretreated with 6-hydroxydopamine, the descending efferent connections of the substantia nigra are restricted to a bilateral projection to the superior colliculus and a pathway which stops in the dorso-lateral reticular formation of the pons.
Abstract: In animals pretreated with 6-hydroxydopamine, the descending efferent connections of the substantia nigra are restricted to a bilateral projection to the superior colliculus and a pathway which stops in the dorso-lateral reticular formation of the pons.
TL;DR: There was a strong correlation between the grade of hepatic coma and CSF IAA, and data indicate that there is an association between elevated CNS tryptamine metabolism and liver dysfunction.
Abstract: Lumbar CSF indoleacetic acid (IAA) was higher in patients with cirrhosis of the liver than in controls. It was also higher in CSF of patients in coma than in those with hepatic cirrhosis but not in coma. There was a strong correlation (r = 0.89, p less than 0.01) between the grade of hepatic coma and CSF IAA. These data indicate that there is an association between elevated CNS tryptamine metabolism and hepatic coma. How far changes in the metabolism of tryptamine and other trace amines are relevant to the induction of hepatic coma or are simply a reflection of advanced liver dysfunction is unclear.
TL;DR: Observations suggest that tyrosine availability can affect both catecholamine synthesis in and release from the sympathoadrenal apparatus.
Abstract: Tyrosine administration to rats causes dose-related increases in urinary catecholamine levels without reducing tissue catecholamines. Pretreatment with carbidopa, a peripheral inhibitor of aromatic-L-amino acid decarboxylase, reduces basal urinary catecholamine levels and blocks the urinary catecholamine increases caused by tyrosine administration or cold exposure. DOPA excretion, which is usually undetectable by our methods, becomes significant after carbidopa, and rises a further four-fold when rats are also given tyrosine. These observations suggest that tyrosine availability can affect both catecholamine synthesis in and release from the sympathoadrenal apparatus.
TL;DR: Tyrosine's effects on catecholamine synthesis and release might be amplified in cortex and hippocampus, where highest relative increases in tyrosine concentrations were observed.
Abstract: Endogenous tyrosine concentrations varied two-fold among various rat brain regions, tending to be highest in brain stem structures. Administration of L-tyrosine (100 mg/kg) increased tyrosine concentrations in all brain areas; high relative increases were observed in areas with low initial tyrosine concentrations and vice versa, resulting in a more uniform distribution of tyrosine in the brain. Largest relative increases were observed in cortex and hippocampus. Tyrosine concentrations in all areas reached maximal levels 1 hour after tyrosine was given and declined gradually over the next 3 hours. The results suggest that tyrosine's effects on catecholamine synthesis and release might be amplified in cortex and hippocampus, where highest relative increases in tyrosine concentrations were observed.
TL;DR: It is suggested that the action of standard MAO-inhibiting drugs may be compounded of two separate actions, usually associated but, in fact, unrelated.
Abstract: Although the selective monoamine oxidase (MAO) inhibitor, (−)-deprenyl, substantially inhibits tyramine-oxidizing ability in the pig, intravenous tyramine challenge after pretreatment with this drug failed to produce the characteristic pressor response (“cheese effect”) associated with other irreversible MAO inhibitors. Conversely, pretreatment with the tyramine oxidation-sparing selective MAO inhibitor, clorgyline, followed by intravenous tyramine, paradoxically resulted in a profound pressor response. We suggest that the action of standard MAO-inhibiting drugs may be compounded of two separate actions, usually associated but, in fact, unrelated.
TL;DR: It may be concluded that January and April are the most active months of those tested for the melatonin/5-methoxytryptophol synthesis in the rat pineal gland.
Abstract: In the pineal of 21-day old male Wistar rats hydroxyindole-O-methyl-transferase (HIOMT) activities involved in the synthesis of several 5-methoxyindoles were determined during the night in April, June, October and January. A high HIOMT activity for the synthesis of melatonin/5-methoxytryptophol was determined in the months of January and April. In June and October a decrease was observed. The activity maxima coincide with peaks of activity found for the synthesis of 5-methoxytryptophan. Synthesis of 5-methoxytryptamine occurred only in June and October, whereas the synthesis of 5-methoxyindole-3-acetic acid occurred only in January. From these results it may be concluded that January and April are the most active months of those tested for the melatonin/5-methoxytryptophol synthesis in the rat pineal gland. A possible physiological role of the 5-methoxyindoles other than melatonin and 5-methoxytryptophol is discussed.
TL;DR: Five Parkinsonian patients with incapacitating and unpredictable “on-off” changes who were free of significant depression were given conventional bilateral ECT while usual drug regimens were maintained.
Abstract: Marked, abrupt and disabling oscillations in motor performance—the “on-off” phenomenon-frequently occur in the course of long-term levo-dopa therapy for Parkinson's disease. Although these fluctuations are usually refractory to available medications it has recently been suggested that electroconvulsive therapy (ECT) may be beneficial.
TL;DR: It is suggested that the high reactivity of SH rats is related to a dysfunction in the noradrenergic neurons in the central nervous system.
Abstract: The binding of3H-WB 4101, anα1-adrenoceptor antagonist, to membranes of the cerebral cortex, the hypothalamus, and the lower brainstem was examined in adult spontaneously hypertensive (SH) rats and in normotensive Wistar Kyoto (WK) controls. The specific binding of3H-WB 4101 (0.33 nM) was significantly higher in homogenates from the cerebral cortex of SH rats as compared to WK rats. No differences were detected between SH and WK rats in the specific binding of3H-spiroperidol (0.25 nM), a dopamine receptor antagonist, to membranes from the corpus striatum and the limbic forebrain. The locomotor activity was significantly higher in SH rats as compared to WK controls, in all probability due to a lack of habituation to environmental change. It is suggested that the high reactivity of SH rats is related to a dysfunction in the noradrenergic neurons in the central nervous system.
TL;DR: Female Wistar rats treated with ethanol produced a reduction of fluid and food consumption and changes in the metabolism of cerebral monoamines, and there was an increase in serotonin (5-HT) turnover statistically significant in the striatum, and a decrease in noradrenaline (NA) turnover in ethanol rats as compared to controls.
Abstract: Female Wistar rats (150–200 g) were treated with ethanol (15% w/v) for 21 days and compared with control rats given water. Ethanol administration produced a reduction of fluid and food consumption and changes in the metabolism of cerebral monoamines. There was an increase in serotonin (5-HT) turnover statistically significant in the striatum, and a decrease in noradrenaline (NA) turnover in ethanol rats as compared to controls. Endogenous NA levels were significantly increased in the diencephalon and dopamine (DA) levels were increased in the striatum. After inhibition of catecholamine synthesis withα-methyltyrosine (α-MT), NA depletion was significantly retarded but no changes in DA depletion were noted. DOPA accumulation after decarboxylation inhibition showed no significant change in any brain region studied.
TL;DR: The results indicate that lithium has a neuroleptlike effect on avoidance behavior, and it is suggested that some of the behavioral effects of lithium may be mediated via interference with central catecholaminergic mechanisms.
Abstract: The effect of a single injection of various doses of lithium chloride was tested on conditioned avoidance behavior and on the accumulation of DOPA and 5-HTP after inhibition of aromatic amino acid decarboxylase. Lithium specifically suppressed conditioned avoidance behavior and reduced formation of DOPA, but not 5-HTP. The behavioral effect of lithium could be completely antagonized with additional L-DOPA treatment. The results indicate that lithium has a neuroleptlike effect on avoidance behavior, and it is suggested that some of the behavioral effects of lithium may be mediated via interference with central catecholaminergic mechanisms.
TL;DR: It is concluded that GABA-ergic mechanisms are involved in central respiratory control in rats lightly anesthetized with halothane and treated with graded intraperitoneal doses of GHBA, a GABA analogue.
Abstract: Rats lightly anesthetized with halothane were treated with graded intraperitoneal doses of gamma-hydroxybutyric acid (GHBA), a GABA analogue. The drug induced a dose dependent decrease in minute ventilation, mainly due to reduced respiratory frequency. A reduced pH in arterial blood was recorded. GHBA also blunted or abolished the respiratory response to CO2 exposure in a dose-related way. Picrotoxin (0.25, 0.5 or 1.0 mg/kg intravenously), a presumed GABA antagonist did not significantly change the respiratory pattern when given alone but clearly antagonized the GHBA-induced respiratory depression. It is concluded that GABA-ergic mechanisms are involved in central respiratory control.
TL;DR: An important retardation in amine disappearance after synthesis inhibition was found for DA and NA in the left hemisphere and to a lesser extent for DA in the right hemisphere, suggesting a reduction of the physiological activity of catecholaminergic neurons.
Abstract: Unilateral brain ischemia was induced in the rat by injecting radioactive microspheres into the left internal carotid artery. The microspheres were mainly distributed in the left cerebral hemisphere which contained 8 to 10 times more microspheres than the contralateral hemisphere. Embolization caused dopamine (DA) and noradrenaline (NA) depletion only in the left hemisphere. NA levels were already reduced 2 hours after injury while DA was still unaltered after 6 hours. A 30--40% depletion was observed for the two amines after 24 hours. Catecholamine turnover was estimated by measuring the amine depletion after synthesis inhibition with alpha-methyl-p-tyrosine. During the first 2 hours following embolization, DA and NA depletions were slightly increased only in the left hemisphere, indicating an increase in catecholamine efflux. At times 24 hours, an important retardation in amine disappearance after synthesis inhibition was found for DA and NA in the left hemisphere and to a lesser extent for DA in the right hemisphere, suggesting a reduction of the physiological activity of catecholaminergic neurons. These biochemical alterations can be related to the post-stroke behavioural changes of the embolized animals which exhibited an initially increased motor activity followed by a lethargic state.
TL;DR: Results from animal experiments support the hypothesis that pineal gland function can influence some aspects of tissue metabolism and glucose homeostasis and contribute to an understanding of indirect routes by which pineal activity can possibly affect the growth and activity of some kinds of tumors.
Abstract: Results from animal experiments support the hypothesis that pineal gland function can influence some aspects of tissue metabolism and glucose homeostasis. Evidence of pineal effects on particular endocrine and sympatheto-adrenal targets contributes to an understanding of indirect routes by which pineal activity can possibly affect the growth and activity of some kinds of tumors, in part through nutrient and metabolic effects in the tissue environment of the tumor cells.