Showing papers in "Journal of Neural Transmission in 1976"
TL;DR: For the first time it could be demonstrated that the time course of nigrostriatal degeneration, independent of the age of the parkinsonian at the beginning of the illness, is linear for the last stage and the denervation progressively increases as the duration of illness progresses.
Abstract: It could be shown that the post mortem analysis of biogenic amines, precursors and metabolites in the human brain are influenced by various parameters. 1. The patient's medical history; long term observations of the course of the disease; age; sex. 2. Terminal illness; duration of terminal illness. 3. Previous treatment with drugs; last drugs. 4. Time interval between last drug treatment and death; time of day and date of last drug consumption. 5. Rapidity of death; time of death; duration of coma. 6. Changes occurring in tissues before death; patients' constitution during terminal illness. 7. Changes in concentration of the biogenic amines, precursors, and metabolites depending on the patient's age. 8. Time between death and necropsy. 9 Dissection of specimen. 10. Period of storage; temperature of storage. 11. Chronbiological rhythm of substances. 12. Methods of assayL 13. Homogeneity of all mentioned parameters in the control group and patient's group. For the first time it could be demonstrated that the time course of nigrostriatal degeneration, independent of the age of the parkinsonian at the beginning of the illness, is linear for the last stage and the denervation progressively increases as the duration of illness progresses.
519 citations
TL;DR: The caudate nuclei and putamens of 30 human brains were analyzed for dopamine and its metabolite 3-methoxytyramine and found that dopamine and the sum declined with the time interval between death and autopsy as well as with age.
Abstract: The caudate nuclei and putamens of 30 human brains were analyzed for dopamine and its metabolite 3-methoxytyramine, most of which was presumably formed from dopamine postmortally. It was found that dopamine and the sum (dopamine + methoxytyramine) but not methoxytyramine declined with the time interval between death and autopsy as well as with age.
320 citations
TL;DR: It was suggested that increased activity of dopamine at central dopamine receptors plays a role in the pathophysiology of this disorder and a defect in negative feedback control mechanisms is more consistent with the known characteristics of anorexia nervosa.
Abstract: Based on a review of the pathophysiology of the major symptoms of anorexia nervosa, it was suggested that increased activity of dopamine at central dopamine receptors plays a role in the pathophysiology of this disorder. Although dopamine receptor site hypersensitivity, or synthesis, of a false transmitter could account for this, a defect in negative feedback control mechanisms is more consistent with the known characteristics of anorexia nervosa. The possible role of pure dopamine antagonists in symptomatic treatment and of dopamine agonists in reversing this disorder was discussed.
108 citations
TL;DR: The highly significant increase of 5-HIAA in Transcendental Meditation technique suggests systemic serotonin as “rest and fulfillment hormone” of deactivation-relaxation and 5-HT (5-hydroxytryptamine, serotonin) is considered to to be the EC-cell (enterochromaffine-cell) hormone requested by Fujita and Kobayashi.
Abstract: The highly significant increase of 5-HIAA (5-hydroxyindole-3-acetic acid) in Transcendental Meditation technique suggests systemic serotonin as "rest and fulfillment hormone" of deactivation-relaxation. Furthermore 5-HT (5-hydroxytryptamine, serotonin) is considered to be the EC-cell (enterochromaffine-cell) hormone requested by Fujita and Kobayashi and its role for EEG synchronisation via area postrema chemoreceptor as anti arousal agent is being discussed. The significant decrease of the catecholamine metabolite VMA (vanillic-mandelic acid) in meditators, that is associated with a reciprocal increase of 5-HIAA supports as a feedback necessity the "rest and fulfillment response" versus "fight and flight". As the adreno medullary tissue serves for hormonal reinforcement of orthosympathetic activity, the Enterochromaffine Cell System (having taken the form of distinct organs in some species as octopus and discoglossus) is suggested to serve via serotonin for humoral reinforcement of parasympathetic activity in deep relaxation.
96 citations
TL;DR: The data support the view that dopamine serves as a transmitter in cortical neurons apart from being a precursor for noradrenaline.
Abstract: The rat cerebral neocortex was sectioned by 3 transverse cuts and analyzed for dopamine and noradrenaline. Dopamine concentration decreased gradually from the rostral (97±4 ng/g) to the caudal (59±2 ng/g) end of the neocortex. Also, the noradrenaline concentration was highest in the rostral part (269±6 ng/g) and decreased gradually reaching a concentration of 238±3 ng/g in the caudal part. Since the quotient dopamine/ noradrenaline showed similar changes in the neocortex parts investigated the data support the view that dopamine serves as a transmitter in cortical neurons apart from being a precursor for noradrenaline.
91 citations
TL;DR: It is concluded that the short-term control of catecholamine synthesis presumably involves two independent feedback mechanisms, one intraneuronal mechanism operating via end-product inhibition, and one synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively.
Abstract: The influence of varying brain levels of dopamine, noradrenaline and 5-HT on their respective synthesis rates has been investigated. The first step in monoamine synthesis was studiedin vivo by measuring the accumulation of dopa and 5-hydroxytryptophan after inhibition of the aromatic L-amino acid decarboxylase. Variations in monoamine levels were obtained by combined treatment with inhibitors of the decarboxylase (NSD 1015 or Ro 4-4602) and of monoamine oxidase (pargyline). An increase in monoamine levels by pargyline was found to inhibit the synthesis of dopamine, noradrenaline and 5-HT. Conversely, a decrease in monoamine levels induced by the decarboxylase inhibitor Ro 4-4602 appeared to stimulate dopamine and noradrenaline synthesis but had no effect on 5-HT synthesis. The influence of varying levels of dopamine and noradrenaline on the synthesis of these amines could still be demonstrated after blockade of dopamine receptors and ofα-adrenergic (noradrenaline) receptors by haloperidol, suggesting that the mechanism involved in this feedback control is mediated via end-product inhibition of tyrosine hydroxylase. On the other hand, the stimulating influence of haloperidol on the synthesis of catecholamines does not seem to be directly related to changes in catecholamine levels. It is concluded that the short-term control of catecholamine synthesis presumably involves two independent feedback mechanisms, one intraneuronal mechanism operating via end-product inhibition, and one synaptic mechanism mediated via dopamine and noradrenaline receptors, respectively. Both pre- and postsynaptic receptors may be involved in the latter mechanism.
70 citations
TL;DR: The flexor reflex in the spinal rat may be a good model to evaluate the effect on the central (spinal cord) serotonin receptor and to differantiate this effect from that on the noradrenaline system.
Abstract: The effects of serotonergic and antiserotonergic drugs on the hind limb flexor reflex (measured as a contraction of musculus tibialis anterior or as a flexion of the paw) in the spinal rat was studied. All serotonergic drugs used (L-5-hydroxytryptophan, L-tryptophan, LSD, fenfluramine, p-chloroamphetamine) stimulate the flexor reflex. Serotonin receptor blockers (cyproheptadine, WA-335, methergoline), which given alone are inactive, inhibit the stimulation induced by serotonergic drugs but do not influence that one caused by noradrenergic agents (amphetamine, clonidine). Both types of stimulation (serotonergic and noradrenergic) are antagonized by noradrenaline receptor blockers (phenoxybenzamine, clozapine). The antiserotonergic action of serotonin antagonists used was confirmed on the basis of the antagonism to the head twitches induced by L-5-hydroxytryptophan. The flexor reflex in the spinal rat may be a good model to evaluate the effect on the central (spinal cord) serotonin receptor and to differantiat this effect from that on the noradrenaline system.
61 citations
TL;DR: Questions about the possible clinical influence of substance P in disease states involving monoaminergic mechanisms including Parkinsonism and schizophrenia are strengthened.
Abstract: Synthetic substance P has been discovered to stimulate significantly the formation of dopa in the limbic, striatum, hemisphere and diencephalon regions of the brain and the lower brain stem. There was no effect upon 5-hydroxytryptophan formation or on tryptophan or tyrosine levels. After inhibition of monoamine synthesis by N′-(DL-seryl)-N2-(2, 3, 4-trihydroxybenzyl)hydrazine, substance P significantly accelerated the disappearance of dopamme, noradrenaline and 5-hydroxytryptamine.
58 citations
TL;DR: The regulatory mechanisms governing the activity of central dopaminergic neurons in the tuberoinfundibular system appear to differ from those in the mesolimbic and nigrostriatal systems.
Abstract: Dopamine synthesis rates were determined in terminals of tuberoinfundibular, mesolimbic and nigrostriatal neuronal systems by observing the decline of dopamine contents in the median eminence, olfactory tubercle and corpus striatum after administration of alpha-methyltyrosine. In control (no drug treatment) animals the rate of synthesis of dopamine was greater in the median eminence than in the other two brain regions. Haloperidol increased and piribedil decreased dopamine turnover in the corpus striatum and olfactory tubercle, but not in the median eminence. Gamma-Butyrolactone increased dopamine concentrations in the olfactory tubercle and striatum without altering the concentration in the median eminence. Thus, the regulatory mechanisms governing the activity of central dopaminergic neurons in the tuberoinfundibular system appear to differ from those in the mesolimbic and nigrostriatal systems.
57 citations
TL;DR: A California series and a large collaborative study throughout the United States show the ratio of observed to expected deaths to be normal, while a New York study with similar patients and a Montreal group of much more severely disabled patients show greater mortality.
Abstract: Excess mortality,i.e. more deaths than expected in a similar normal population, has been reduced in Parkinson's disease by levodopa. A California series and a large collaborative study throughout the United States show the ratio of observed to expected deaths to be normal. In contrast, a New York study with similar patients and a Montreal group of much more severely disabled patients show greater mortality. The reasons for these differences are unclear, but some variation in results may be attributed to different methods of calculating expected deaths to derive the ratio of observed to expected deaths.
55 citations
TL;DR: In this paper, the diurnal variations of dopamine-β-hydroxylase activity (DBH) and concentrations of homovanillic acid (HVA) and 3-methoxy-4hydroxyphenylglycol (MHPG) were measured in serum of 11 normal volunteers at 8 a.m., 2 p.m. and 2 am.
Abstract: Dopamine-β-hydroxylase activity (DBH) and concentrations of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in serum of 11 normal volunteers at 8 a.m., 2 p.m., 8 p.m. and 2 a.m. DBH was higher at 8 a.m. (p<0.05) and lower at 2 a.m. (p< 0.0025). MHPG followed the same course, while HVA was higher at 8 p.m. (p<0.05). The mean values for the eleven volunteers were: DBH 65.8±25.8 nanomoles hydroxylated tyramine per ml serum and hour (at substrate concentration 0.05 mM), HVA 89.9±57.3 ng/ml serum and MHPG 10.9±3.4 ng/ml, with variation coefficients of 38.6, 63.8 and 30.1 respectively. The circadian variations found in serum parallel the data from estimations of MHPG and HVA in urine by other investigators. It is suggested that the diurnal variations of DBH, MHPG and HVA reflect the alternating activity of the catecholaminergic neurons in the peripheral as well as the central nervous system.
TL;DR: Levels of free and conjugated monoamine metabolites were analysed in brain tissue of rat and man and the major dopamine metabolite found in this human brain was HVA.
Abstract: Levels of free and conjugated monoamine metabolites were analysed in brain tissue of rat and man. In the rat the conjugates were mainly of the sulfate ester type. The levels of conjugated dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) constituted 40—50% of the total amount of the metabolites. 4-Hydroxy-3-methoxy-phenylglycol (HMPG) and 5-hydroxy-3-indoleacetic acid (5-HIAA) were present as conjugates in 90 and 10% of the total levels. Chlorpromazine treatment resulted in an elevation of both the free and the conjugated forms of the dopamine metabolites and HMPG. In a human caudate nucleus obtained at autopsy both DOPAC and HMPG were present in the free form and as sulfate and glucuronide conjugates. The major dopamine metabolite found in this human brain was HVA. This metabolite and 5-HIAA occurred predominantly as free metabolites.
TL;DR: The possibility that malfunction of the enzyme monoamine oxidase (E.C.4.4., MAO) could lead to aberrations in the catabolism of biogenic amines in the central nervous system and give rise to certain mental abnormalities is explored.
Abstract: This article explores the possibility that malfunction of the enzyme monoamine oxidase (E.C. 1.4.3.4., MAO) could lead to aberrations in the catabolism of biogenic amines in the central nervous system and give rise to certain mental abnormalities. No conclusive evidence could be presented to substantiate this. Data on the normal function of the enyzme (for example its existence in multiple forms, the control of MAO activity by hormones or the independent development of MAO activities towards different substrates during maturation) are reviewed.
TL;DR: The results obtained indicate a facilitatory role of histamine on prolactin release, which seems to be specific and not mediated by other neurotransmitters.
Abstract: Histamine injected into the 3rd ventricle of normal male rats at doses of 5–60μg (free base) caused a marked release of prolactin. Responses were prevented by the antihistamine chlorpheniramine but not by atropine, methysergide or phenoxybenzamine. It thus seems that effects of histamine on prolactin are specific and not mediated by other neurotransmitters. Plasma LH remained normal after injection of low doses but it was decreased after high doses. The results obtained indicate a facilitatory role of histamine on prolactin release.
TL;DR: It is conjecture that the action of L-dopa on parkinsonian patients is twofold: L- dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity.
Abstract: Since there is substantial evidence for a nigrostriatal dopamine defect in Parkinson's disease and since monoamine oxidase (MAO) appears to be essential for the degradation of dopamine, we investigated whether this enzyme is involved in the pathogenesis of this disease or in the therapeutic action of L-dopa. To gain a solid basis for our analysis we studied some properties of platelet MAO, at present the only practicalin vivo source for human MAO. Substrate and inhibitor pattern clearly pointed to a predominant B-type character of this enzyme. By using 3 substrates, m-iodobenzylamine, p-methoxybenzylamine, and tyramine, we found a marked age and sex difference in MAO activity. In untreated parkinsonian patients, platelet MAO was slightly reduced as compared with age- and sex-matched controls. Treatment with L-dopa induced a further reduction of platelet MAO activity in both sexes, but more in men than in women. We conjecture that the action of L-dopa on parkinsonian patients is twofold: L-dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity. Dopamine, formed from L-dopa, may thus have a better chance for survival in reaching the dopaminergic receptor.
TL;DR: It is suggested that “synaptic” ribbons of rat pinealocytes, far from being phylogenetic relics of no functional significance play a role in the function of the pineal organ.
Abstract: A quantitative study of “synaptic” ribbons in rat pinealocytes was performed after orchidectomy and in organ culture Both orchidectomy and culturing the pineal organ caused an increase in number and size of these structures
TL;DR: The application of apomorphine to the nucleus accumbens, but not to the neostriatum, enhanced the accumulation of 5-hydroxytryptophan in the central nervous system following inhibition of the aromatic L-amino acid decarboxylase.
Abstract: Apomorphine (10μg) was injected bilaterally into the nucleus accumbens or the neostriatum of rats. The application of apomorphine to the nucleus accumbens, but not to the neostriatum, enhanced the accumulation of 5-hydroxytryptophan in the central nervous system following inhibition of the aromatic L-amino acid decarboxylase. The effect was greatest in the brain stem, particularly in the pons plus medulla oblongata. Similar but smaller rises were observed for the accumulation of DOPA in noradrenalinerich regions. The motor activity was increased and the body temperature was decreased by apomorphine in the nucleus accumbens, whereas smaller or no effects were obtained from the neostriatum.
TL;DR: Withdrawal of the L-Dopa therapy for a few days in 13 patients provided strong evidence that it is due to the progression of the disease and to a partial loss of L- Dopa efficacy.
Abstract: 35 parkinsonian patients have been treated over 3 years with L-Dopa combined with benserazide. After an impressive improvement during the first months of treatment a slow but significant deterioration of the patients' condition was observed. At the end of the observation period however their condition was still significantly better than before starting the treatment. A reduced mean L-Dopa dosage was ruled out as the cause of this deterioration. Withdrawal of the L-Dopa therapy for a few days in 13 patients provided strong evidence that it is due to the progression of the disease and to a partial loss of L-Dopa efficacy.
TL;DR: Evidence is given of diurnal rhythms in the mean number of dense-core vesicles surrounding a Golgi complex in the perikaryon of light rabbit pinealocytes and of those present per terminal of light pinealocyte processes.
Abstract: Evidence is given of diurnal rhythms in the mean number of dense-core vesicles surrounding a Golgi complex in the perikaryon of light rabbit pinealocytes and of those present per terminal of light pinealocyte processes. These rhythms show their top at noon and in the evening, respectively.
TL;DR: Pretreatment of rats with AOAA raised the concentration of rat brain GABA and inhibited the hyperactivity produced by increasing brain 5-hydroxytryptamine (5-HT) concentration by administration of tranylcypromine and L-tryptophan, suggesting that post-synaptic 5-HT responses were being inhibited.
Abstract: Pretreatment of rats with aminooxyacetic acid (AOAA; 40 mg/kg) raised the concentration of rat brain GABA and inhibited the hyperactivity produced by increasing brain 5-hydroxytryptamine (5-HT) concentration by administration of tranylcypromine and L-tryptophan. The maximum effect was seen 90 min after AOAA injection with smaller effects 30 and 180 min after injection. AOAA did not affect the rate of 5-HT accumulation in the brain, but did inhibit the hyperactivity response which follows injection of the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine, suggesting that post-synaptic 5-HT responses were being inhibited. AOAA also inhibited the locomotor activity which follows administration of tranylcypromine and L-dopa. Blockade of GABA receptors by injection of picrotoxin (2.5 mg/kg) enhanced the dopamine hyperactivity. Since a dopaminergic system has been shown to be involved in the 5-HT hyperactivity syndrome and appears to act post-synaptically to the 5-HT neurones initiating the syndrome it is suggested that inhibition of the 5-HT hyperactivity syndrome may be due to accumulation of GABA distal to the dopaminergic receptors.
TL;DR: Different areas of the brain and the pituitary gland, namely the parietal cortex, the pre-optic region (POA), the median eminence, the medial basal hypothalamus without the Median eminence and the posterior pituitsary contain different concentrations of DA and NE, emphasizing the importance of regional analyses in tissue amines determination.
Abstract: A rapid and simple procedure to determine Dopamine (DA) and Norepinephrine (NE) in small tissue samples (μg quantities) is described. The radioenzymatic assay sensitivity, defined as twice the blank, is about 0.1 ng for NE and DA. Drugs known to modify brain catecholamine metabolism were shown to alter differentially DA and NE concentration in the medial basal hypothalamus (MBH) of male rats. Different areas of the brain and the pituitary gland, namely the parietal cortex, the pre-optic region (POA), the median eminence (ME), the medial basal hypothalamus without the median eminence and the posterior pituitary contain different concentrations of DA and NE, emphasizing the importance of regional analyses in tissue amines determination.
TL;DR: The isolated perfused chicken heart is at present a unique tool for studying the output of the parasympathetic transmitter in the absence of cholinesterase inhibition.
Abstract: In chicken hearts, the acetylcholine (ACh) output in response to vagal stimulation was easily detectable by gas chromatography even in the absence of cholinesterase inhibition. Eserine 10−6 M markedly increased the ACh output. In contrast, the ACh output from the perfused rabbit heart was not measurable in the absence of cholinesterase inhibition. Both ACh concentration and cholinesterase activity were higher in the chicken heart than in the rabbit heart. In conclusion, the isolated perfused chicken heart is at present a unique tool for studying the output of the parasympathetic transmitter in the absence of cholinesterase inhibition.
TL;DR: Catecholamine neurons were found in the periventricular nucleus, arcuate nucleus, and a region around the mammillothalamic tract in the hypothalamus of the squirrel monkey, and exhibited fluorescence only after intraventricular injections of alpha-methyl-norepinephrine.
Abstract: Catecholamine neurons were found in the periventricular nucleus, arcuate nucleus, and a region around the mammillothalamic tract in the hypothalamus of the squirrel monkey. These neurons did not fluoresce in control or monoamine-oxidase-inhibited animals, and exhibited fluorescence only after intraventricular injections of alpha-methyl-norepinephrine. Dense accumulations of catecholamine varicosities appeared in the periventricular nucleus, external contact zone of the median eminence, and perivascular region of the median eminence; the arcuate nucleus contained no more than a moderate density of catecholamine varicosities. The median eminence fluorescence had a regional character, with greatest intensity in the caudal portion.
TL;DR: A direct neurophysiological evidence for the blockade of DA-receptors by antipsychotic drugs is rendered in correspondence to their clinical efficacy and agree with data from clinical observations and obtained in neurochemical, behavioral and indirect neurophysiology experiments.
Abstract: The effect of antipsychotic drugs was tested on responses to micro-electrophoretically applied dopamine, acetylcholine and 5-hydroxy-tryptamine in identified neurons of the marine gastropod Aplysia californica. Fluphenazine was able to depress the response to DA in concentration of 10μM, with 100μM DA-responses of many neurons were blocked completely. Thioridazine (10 and 100μM) and haloperidol (50μM) were also effective in depressing DA-responses, while the non-antipsychotic phenothiazines mepazine (10 and 100μM) and promethazine (100μM) had only a slight action on DA-receptors. ACh-and 5-HT-responses were slightly affected only by high concentrations after long lasting perfusion. The investigated drugs had no persistent or only an insignificant effect on resting membrane potential and amplitude of action potentials of the neurons. With haloperidol depolarizing afterpotentials leading to double discharges were observed in some neurons. In a few instances spontaneous EPSPs disappeared with the DA-response under the influence of anti-psychotic drugs. The results render a direct neurophysiological evidence for the blockade of DA-receptors by antipsychotic drugs in correspondence to their clinical efficacy and agree with data from clinical observations and obtained in neurochemical, behavioral and indirect neurophysiological experiments.
TL;DR: Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. as discussed by the authors showed that several distinct peaks could be detected showing excitation and fluorescence maxima resembling those of indoles.
Abstract: Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. A low molecular Sephadex G-25 fraction F4 was filtrated on Sephadex G-10. Several distinct peaks could be detected showing excitation and fluorescence maxima resembling those of indoles. A thinlayer chromatography study revealed that one Sephadex G-10 peak contained a spot identical with that of synthetic 5-methoxytryptophol, another a spot with the same Rf-values in different solvents as synthetic 5-hydroxytryptophol, while from a third peak a substance was isolated identical with synthetic melatonin. Mass spectra of the isolated compounds were recorded. These results are compared with those of previous isolation studies.
TL;DR: It was found that the injection of a small dose of L-Dopa did not reverse the catalepsy produced by the short-acting dopamine depleter, Ro 4-1284, and it was suggested that under normal conditions the slow transfer of stored dopamine to a releasable site is sufficiently rapid to maintain striatal function.
Abstract: Previous studies have provided evidence for the prime importance of newly synthesized dopamine as compared with the large endogenous stores of amine in the functional mobilization of dopamine under conditions of a heavy demand on the neuron such as in the presence of a neuroleptic. The present study was designed to examine the role of storage granules in the utilization of newly synthesized dopamine and to examine the mechanism of the cataleptic action of reserpine-like drugs. It was found that the injection of a small dose of L-Dopa did not reverse the catalepsy produced by the short-acting dopamine depleter, Ro 4-1284, either when the depleter was given alone or was given after tyrosine hydroxylase blockade byα-methyltyrosine, provided that the L-Dopa was given at a time when Ro 4-1284 was present. However, the same dose of L-Dopa quickly reversed catalepsy when given at a time of dopamine depletion but in the absence of Ro 4-1284. Sinceα-methyltyrosine alone does not produce catalepsy until exhaustion of the large endogenous dopamine pool, but quickly potentiates neuroleptic-induced catalepsy, it is suggested that under normal conditions the slow transfer of stored dopamine to a releasable site is sufficiently rapid to maintain striatal function. However, the transfer rate appears to be too slow for adequate mobilization of the store under conditions of a heavy demand. It is further suggested that a prime role of storage granules is to channel newly synthesized dopamine into the synaptic cleft. Reserpine-like drugs appear to produce catalepsy, not by depletionper se of the main dopamine pool, but by interference with this granule channeling function.
TL;DR: The cardiovascular effects of GHBA are suggested to be of central origin, and possibly involve central noradrenergic mechanisms.
Abstract: Gammahydroxybutyric acid (GHBA) 1 g/kg i.p. induced a marked and sustained increase in heart frequency and blood pressure in the rats. These effects of GHBA were abolished by a high spinal transection. In biochemical experiments GHBA in the same dose increased the turnover of brain noradrenaline but decreased the turnover of dopamine. The cardiovascular effects of GHBA are suggested to be of central origin, and possibly involve central noradrenergic mechanisms.
TL;DR: The functional integrity of granular DA binding and releasing mechanisms appears to be a pre-requisite for the antagonism between GHB and Amph, and the GHB-Amph antagonism may be of a functional nature.
Abstract: D-Amphetamine (Amph) and p-chloroamphetamine (PCA) induced dose-dependent increases in oropharyngeal myocloniform twitch activity (MTA) in rats anesthetized with urethane. In doses of 80-120 mg/kg, gamma-hydroxybutyric acid (GHB) blocked Amph-induced MTA. The blockade was readily surmountable. Pretreatment with reserpine markedly enhanced the myoclonigenic effect of Amph and rendered it insensitive blockade by GHB, 160 mg/kg. PCA and tryptamine also effectively stimulated MTA, but unlike Amph were antagonized by low doses of the serotonin (5-HT) antagonist methysergide. In doses which blocked Amph, GHB failed to antagonize the myoclonigenic effect of PCA. It is concluded that: (a) the actions of Amph and PCA on MTA is less sensitive to GHB blockade than DA-mediated MTA; and (c) the GHB-Amph antagonism may be of a functional nature, i.e. result from a depression of the firing activity of DA neurons produced by GHB. Since reserpinization abolished the GHB effect on Amph-induced MTA, the functional integrity of granular DA binding and releasing mechanisms appears to be a pre-requisite for the antagonism between GHB and Amph.
TL;DR: The morphine-induced cardiovascular depressive effects are primarily elicited by activation of opiate receptors, however, the inhibition of brain NA neurotransmission by morphine appears critically involved in the mediation of the circulatory depression.
Abstract: Morphine caused in the anaesthetized rat reduction in brain noradrenaline (NA) turnover, hypotension and bradycardia, similarly to the antihypertensive,α-adrenergic agonist, clonidine. All effects of morphine were antagonized by naloxone, as well as theα-receptor antagonist, yohimbine. In contrast, naloxone did not affect the circulatory depression and reduction in brain NA utilization by clonidine, which both previously have been found to be antagonized by yohimbine. In contrast to clonidine, morphine even in high doses did not facilitate the flexor reflex activity of acutely spinalized rats. Pretreatment with protriptylin largely attenuated the circulatory depressive effects of morphine, as it has previously been found to block the corresponding effects of clonidine. Thus, the morphine-induced cardiovascular depressive effects are primarily elicited by activation of opiate receptors. However, the inhibition of brain NA neurotransmission by morphine appears critically involved in the mediation of the circulatory depression.
TL;DR: Further purification of this active principle of an inhibiting principle acting on the anterior hypophysis of male rats in vitro is described by paper chromatography in two different solvents.
Abstract: Previously we were able to isolate by simple and mild methods from an aqueous sheep pineal extract an inhibiting principle acting on the anterior hypophysis of male ratsin vitro. This substance could be located by paper electrophoresis. In the present paper we describe the further purification of this active principle by paper chromatography in two different solvents. In two regions possessing a special fluorescence an inhibiting factor of the gonadotropic activity of the anterior pituitary was foundin vitro.