Showing papers in "Journal of Neural Transmission in 1984"
TL;DR: The heterogeneous distributions of CABS are suggestive of a neuronal localization, an idea supported by lesion experiments, and does not correlate with indexes of brain blood flow, regional glucose utilization or the distributions of receptor binding sites for drugs and neuro-transmitters analyzed.
Abstract: An in vitro autoradiographic technique has been used for the quantitative mapping of calcium antagonist binding sites (CABS) in the rat brain, using the 1,4-dihydropyridines [3H]PN 200-110 and [3H]PY 108-068 as ligands. CABS were distributed throughout the brain in a highly heterogeneous fashion. The highest densities of CABS were observed in the olfactory bulb, hippocampus and parts of the amygdala. The neocortex was also rich in CABS. The basal ganglia, thalamus and hypothalamus presented intermediate levels of CABS while low densities of sites were seen in areas such as the cerebellum, pons and white matter tracts. The distributions of CABS in brain does not correlate with indexes of brain blood flow, regional glucose utilization or the distributions of receptor binding sites for drugs and neurotransmitters analyzed until now. No correlation exists between CABS distribution and that of any neurotransmitter or brain enzyme described so far. The heterogeneous distributions of CABS is suggestive of a neuronal localization, an idea supported by lesion experiments.
139 citations
TL;DR: Analysis of catecholamine decline after tyrosine hydroxylase inhibition and metabolite/monoamine ratios, as indices for transmitter utilization rate, indicated an increased noradrenaline turnover in terminals spared by DSP 4, while dopamine turnover appeared to be reduced in many regions.
Abstract: Regional effects of DSP 4 on monoamine neurons have been analyzed by chemical assay of endogenous monoamines and their metabolites in rat CNS. The results confirmed that the neurotoxic action of DSP 4 is predominantly on noradrenaline nerve terminal projections originating fromlocus coeruleus, with the most marked effects on terminal fields localized most distant from the noradrenaline perikarya. DSP 4 treatment (10 days) caused no alteration of the regional DA levels, except in cingulate cortex, where a moderate increase (+ 40 %) was observed, possibly at least partially related to a sprouting of dopamine nerve terminals following the noradrenaline denervation. 5-hydroxytryptamine levels were generally unaltered after DSP 4, except for an about 10–25% reduction in cerebral cortex and hippocampus. There was with time a certain noradrenaline recovery, most likely related to regeneration of noradrenaline nerve terminals, although this process was relatively slow (months). Analysis of catecholamine decline after tyrosine hydroxylase inhibition and metabolite/monoamine ratios, as indices for transmitter utilization rate, indicated an increased noradrenaline turnover in terminals spared by DSP 4, while dopamine turnover appeared to be reduced in many regions (i.a. cerebral cortex, striatum, accumbens, olfactory tubercle and spinal cord), most pronounced in cingulate cortex. The results indicate that noradrenaline neurons have a facilitatory action on dopamine neurons. The DSP 4 treatment did not cause any significant effect on 5-hydroxytryptamine turnover in any of the individual regions analyzed.
98 citations
TL;DR: Changes in norepinephrine, epinephrine, dopamine, dopamine and serotonin levels in adult normal animals after treatment with the tryptophan hydroxylase inhibitor and after the intraventricular administration of 6-hydroxydopamine or 5, 7-dihydroxytryptamine are discussed.
Abstract: The norepinephrine (NE), epinephrine (EPI), dopamine (DA) and serotonin (5-HT) contents were measured radioenzymatically in seven anatomically defined regions (frontal cerebral cortex, hippocampus, hypothalamus, midbrain, pons-medulla oblongata, cerebellum and spinal cord) in adult normal animals, after treatment with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (p-CPA), and after the intraventricular administration of either 6-hydroxydopamine (6-OHDA) or 5, 7-dihydroxytryptamine (5, 7-DHT). The effects of p-CPA seemed not restricted to 5-HT, since reductions in catecholamine (CA) content were detected in several regions. After 5, 7-DHT given under desimipramine (DMI) protection, comparable reductions in 5-HT levels were obtained but the changes in CA were less severe than after p-CPA. The neurotoxin 6-OHDA decreased the CA in all regions but also 5-HT content in hippocampus, hypothalamus and ponsmedulla. The significance and the interpretation of these changes are discussed in relation to the specificity of the drugs employed, together with an assessment of the local monoamine turnover and the possible functional effects of monoamine interactions in the CNS.
79 citations
TL;DR: The results presented suggest that the AD given repeatedly are able to increase the responsiveness of the brain DA system, probably the mesolimbic one.
Abstract: The effect of repeated treatment (twice a day for 14 days) with antidepressant drugs (AD): imipramine, amitriptyline, zimelidine, citalopram and mianserin on the behavioural response to apomorphine in rats (open field test) was investigated. AD studied, given alone in a single dose or repeatedly, do not change the rats behaviour. A repeated but not single-dose treatment with AD facilitates the behaviour stimulation induced by apomorphine. This facilitation is observed 2 hours after the last dose of imipramine, zimelidine, citalopram and mianserin but 72 hours after the last dose of amitriptyline.
78 citations
TL;DR: It is concluded that this combined treatment has a potent antidepressive action based on the accumulation of l-phenylethylamine in the brain.
Abstract: The antidepressive efficacy of l-deprenyl (5–10 mg daily) plus l-phenylalanine (250 mg/day) has been evaluated in 155 unipolar depressed patients. Both oral and intravenous administration showed beneficial effects in 90% of outpatients and 80.5% of inpatients. It is concluded that this combined treatment has a potent antidepressive action based on the accumulation of l-phenylethylamine in the brain.
74 citations
TL;DR: It could be shown that all investigated 1,4-dihydropyridines after i.p.v. administration can readily enter brain and heart tissue and suggest that PY 108-068 can interact with its binding sites also in vivo.
Abstract: The binding properties of the tritiated calcium channel antagonists PY 108-068 and PN 200-110 were investigated in membrane fractions from rat brainin vitro. Both ligands reversibly interact with one apparent population of stereoselective binding sites which have pharmacological properties described for calcium channel binding sites. In a calcium buffer enhancement of [3H]PY 108-068 binding is observed with an EC50 at pCa 6.28 [3H]PN 200-110 binding is less sensitive to allosteric stimulation by diltiazem and to allosteric inhibition by verapamil and D 600 than [3H]PY 108-068 binding, suggesting that the former ligand may stabilize a high affinity configuration of the binding sites. Afteri.v. administration of [3H]PY 108-068in vivo binding to membranes is observed in brain and heart, which, in contrast to total tissue radioactivity is sensitive to inhibition by unlabelled (+) PN 200-110. These observations suggest that PY 108-068 can interact with its binding sites alsoin vivo. The results ofex vivo binding studies in brain and heart with [3H]PY 108-068 confirm and extend these observations. It could be shown that all investigated 1,4-dihydropyridines (PY 108-068, PN 200-110, nifedipine, Bay K 8644) after i.p. administration can readily enter brain and heart tissue.
74 citations
TL;DR: Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID, and there were no significant differences in SynapsIn I levels between patients and controls in any of the other four brain regions examined.
Abstract: Synapsin I (Protein I), a neuron-specific phosphoprotein enriched in presynaptic nerve terminals, has been used as a quantitative marker for the density of nerve terminals in five brain regions (caudate nucleus, cingulate gyrus, hippocampus, mesencephalon and putamen) from patients who had suffered from Alzheimer disease/senile dementia of Alzheimer type (AD/SDAT), from patients with multi-infarct dementia (MID), and from age-matched controls. Samples were obtained at autopsy. Lower levels of Synapsin I were observed in the hippocampus of patients with AD/SDAT but not with MID. There were no significant differences in Synapsin I levels between patients and controls in any of the other four brain regions examined.
66 citations
TL;DR: The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number ofβ-adrenoceptors and 5-HT2 binding sites in the cerebral cortex produced by long-term treatment of rats with antidepressant drugs was examined.
Abstract: The dependence of intact noradrenergic and serotonergic nerve terminals for the decrease in the number ofβ-adrenoceptors and 5-HT2 binding sites in the cerebral cortex produced by long-term treatment of rats with antidepressant drugs was examined. Noradrenergic nerve terminals were destroyed with the selective noradrenaline neurotoxin DSP4, and serotonergic nerve terminals were destroyed with p-chloroamphetamine (PCA). It was found that lesioning of the noradrenergic nerve terminals abolished the decrease inβ-adrenoceptors produced by desipramine, mianserin and zimeldine and partially antagonized that of theβ-adrenoceptor agonist clenbuterol. PCA pretreatment did not antagonize the long-term effects on theβ-adrenoceptor produced by these compounds. Lesioning of serotonergic nerve terminals affected the down-regulation of 5-HT2 binding sites produced by long-term treatment with mianserin, desipramine and amiflamine. DSP4 pretreatment partially abolished the down-regulation of 5-HT2 binding sites produced by long-term treatment with desipramine, while the effects of mianserin and amiflamine were unaffected by pretreatment with DSP4.
54 citations
TL;DR: Results show that changes in thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function and there appear to be T3-induced changes inβ-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.
Abstract: The effect of thyroid status on noradrenergic synaptic function in the mature rat brain was examined by measuring presynapticα2- and post-synapticβ-adrenoceptors. Repeated triiodothyronine (T3) administration to rats (100μg/kg×14 days: hyperthyroid) caused an 18% increase in striatalβ-adrenoceptors as shown by [3H]-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propyl-thiouracil, PTU×14 days) produced significant 12% and 30% reductions in striatal and hypothalamicβ-adrenoceptors respectively with no change in the cerebral cortex. Presynapticα2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynapticα2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynapticα2-adrenoceptor function. These results show firstly that changes in thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function. Secondly, there appear to be T3-induced changes inβ-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.
51 citations
TL;DR: Alaproclate was found to display a regional selectivity in blocking 5-HT uptake in vivo (measured with the H 75/12-method) and was most potent in the hippocampus and hypothalamus followed by striatum and cerebral cortex with a low potency in the spinal cord.
Abstract: Alaproclate, a new specific 5-HT uptake inhibitor, was examined for its action on several receptors in the brain, for its action on the NA, DA and 5-HT uptake mechanismsin vivo and for its action on brain biogenic amine content. Alaproclate was practically devoid of action on a number of receptors as examined in binding studiesin vitro: 5-HT, histamine-H1,α1,-α2-adrenergic and dopamine D2 receptors. Alaproclate had also a weak affinity for3H-norzimeldine binding sites in contrast to imipramine. Unlike the tricyclic antidepressants alaproclate had a negligible action on muscarinic receptors and failed to block muscarinic induced stimulationin vivo. Contrary to clomipramine alaproclate failed to block NA uptakein vivo. Alaproclate was found to display a regional selectivity in blocking 5-HT uptakein vivo (measured with the H 75/12-method). The compound was most potent in the hippocampus and hypothalamus followed by striatum and cerebral cortex with a low potency in the spinal cord. The results are discussed in relation to a previously presented carrier site model for serotonin reuptake.
50 citations
TL;DR: The results indicate that DA autoreceptor agonists are able to stimulate postsynaptic DA receptors in conditions without endogenous transmitter supply for at least 4–7 days, but not after chronic receptor blockade in a similar period.
Abstract: The motor effects of some DA autoreceptor agonists and apomorphine in rats with bilateral 6-hydroxydopamine lesions of the median forebrain bundle were studied. Whereas (−)-3-PPP, (+)-3-phenethyl-PP and EMD 23448 decreased motility in sham-operated controls, a pronounced hypermotility was induced in 6-OHDA-lesioned rats. 3-PPP enantiomers and apomorphine had similar potency as that found in test models for DA autoreceptor activity in normal rats,e.g. motility inhibition. The DA receptor involvement in the effect of (−)-3-PPP was confirmed by neuroleptic antagonism. (−)-3-PPP and EMD 23448 had similar intrinsic activity as apomorphine, whereas (+)-3-phenethyl-PP and (+)-3-PPP had lower maximal effect. However, the DA autoreceptor agonists differed from apomorphine: The development of postsynaptic supersensitivity to these drugs appeared 4–7 days after the lesion compared to 1–2 days for apomorphine and (+)-3-PPP. Furthermore, no active oral stereotypy was induced by the autoreceptor selective compounds in contrast to the effect observed after apomorphine and (+)-3-PPP. In a separate experiment using circling behaviour in unilaterally 6-OHDA-lesioned rats the different time-course of appearance of supersensitivity to (−)-3-PPP, (+)-3-PPP and apomorphine was confirmed. After chronic reserpine treatment a similar postsynaptic supersensitivity to (−)-3-PPP was observed with a development time between 4 and 7 days and with a similar intensity as that observed in 6-OHDA-lesioned rats. In contrast, after chronic neuroleptic treatment for 12 days, (−)-3-PPP was unable to induce hyperactivity 3–7 days after withdrawal. The results indicate that DA autoreceptor agonists are able to stimulate postsynaptic DA receptors in conditions without endogenous transmitter supply for at least 4–7 days, but not after chronic receptor blockade in a similar period. This should lead to consideration of DA autoreceptor agonists as potential antiparkin-sonian drugs without stimulant effects on normosensitive postsynaptic DA receptors.
TL;DR: It is suspected that the rat pineal gland during day-time is not very susceptible to ambient factors of normal range, as assessed by measuring pineal serotonin-N-acetyltransferase activity (NAT) which is directly proportional to melatonin formation.
Abstract: The present study deals with the question as to what extent the sympathetically innervated rat pineal gland is affected by a number of short-term exogenous stimuli given during day-time, as assessed by measuring pineal serotonin-N-acetyltransferase activity (NAT) which is directly proportional to melatonin formation. In male Sprague-Dawley rats kept under LD 12∶12 pineal NAT was statistically significantly depressed by physical immobilization for 2 hours, swimming for 15 min in water of 10 and 30 °C, exposure for 2 hours to cold (5 °C) or heat (40 °C), noise (90 db) for 2 hours and hunger for 17 hours. An increase in NAT was noted after swimming for 15 min in water of 20 °C. No effect was detectable after 17 hours of thirst or hunger combined with thirst and in one of 2 experiments involving exposure to heat (40 °C, 2 hours) and insulin-induced hypoglycemia. In animals kept under continuous illumination for 48 hours, immobilization resulted in a slightly smaller decrease than under LD 12∶12 and insulin-induced hypoglycemia led to a striking increase of NAT. As the changes in pineal NAT are brought about by rather strong exogenous stimuli it is suspected that the rat pineal gland during day-time is not very susceptible to ambient factors of normal range.
TL;DR: The results of the present study are supportive of the view that 8-OH-DPAT has dopamine agonist, as well as 5-HT agonists, properties.
Abstract: 8-OH-DPAT (8-hydroxy-2-[di-n-propylamino] tetralin) is a novel aminotetralin derivative which has been proposed to be a serotonin (5-HT) agonist devoid of dopamine agonist effects. We now report that the administration of 8-OH-DPAT, like known 5-HT agonists, produced a rapid elevation of serum prolactin concentrations in male rats. The prolactin response to 8-OH-DPAT, like that induced by other 5-HT agonists, was greatly potentiated in animals pretreated with the tryptophan hydroxylase inhibitor, para-chlorophenylalanine. However, the 8-OH-DPAT-induced elevation of serum prolactin cocentrations in untreated rats was not dose-dependent and was modest in magnitude compared to that produced by known 5-HT agonists. In contrast to the stimulatory effects of 8-OH-DPAT on prolactin secretionin vivo 8-OH-DPAT suppressed the secretion of prolactin from anterior pituitary tissuein vitro, and this effect was blocked by haloperidol. The results of the present study are supportive of the view that 8-OH-DPAT has dopamine agonist, as well as 5-HT agonist, properties.
TL;DR: Damage to both dopaminergic and noradrenergic neurons has been shown in the brains of mice, though in a higher dose range than previously shown.
Abstract: N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP), a recently identified neurotoxic compound, has been found to produce destruction of the nigrostriatal dopaminergic neurons in man and monkeys (Langston et al., 1983, Burns et al., 1983). Damage to both dopaminergic and noradrenergic neurons has been shown in the brains of mice, though in a higher dose range (Hallman, 1984). In order to further elucidate the action of NMPTP we have studied the acute effects of the agent in mice.
TL;DR: The data suggest that the increased concentrations of DA metabolites after ethanol is secondary to enhanced DA synthesis and turnover, suggesting an increased synthesis of DA.
Abstract: The effect of acute ethanol on the levels of NE, DA and its metabolites DOPAC and HVA, as well as on the levels of GABA, in the corpus striatum and hypothalamus were investigated in mice in the first two hours after acute ethanol administration. There was a marked increase in the concentration of DOPAC and HVA in the corpus striatum from 30 to 120 minutes after a dose of 3.5 g/kg of ethanol even though the concentration of DA was only elevated at 60 minutes after ethanol. A dose of 1.75 g/kg of ethanol did not increase DA levels 60 minutes after administration although it did increase the concentration of DOPAC and HVA at this time. In the hypothalamus a dose of 3.5 g/kg of ethanol did not change the concentration of NE or DA but did produce a marked increase in the levels of DOPAC and HVA at 60 and 120 minutes post ethanol. A lower dose of ethanol, 1.75 g/kg, produced the same effect 60 minutes after ethanol. Ethanol caused a dose-dependent accumulation of DOPA in the corpus striatum after inhibition of DOPA-decarboxylase suggesting an increased synthesis of DA. These data suggest that the increased concentrations of DA metabolites after ethanol is secondary to enhanced DA synthesis and turnover. The concentration of NE and GABA in the hypothalamus and the corpus striatum was unchanged at any time period after ethanol.
TL;DR: It could be concluded that the “on-off” phenomenon in Parkinson's disease, at least partly, is due to oscillations in the concentration of dopa in plasma, and the introduction of a slow release preparation of dopamine is urgently warranted.
Abstract: To investigate the relation between "on-off" fluctuations in symptomatology and bioavailability of dopa in patients with Parkinson's disease, five Parkinsonian patients with pronounced "on-off" symptoms were studied. Continuously during the study the degree of disability in the patients was registered. Every one hour, and in addition, whenever there was a change from "on" to "off" or vice versa, a blood sample was collected for dopa determination. Since dopa is transported from plasma into the brain by a saturable carrier for which it has to compete with endogenous large neutral amino acids (LNAA), the concentrations of these competitors were measured too. In four of the patients there were considerable oscillations in the plasma dopa concentration during the day; in one of these patients the highest value was as much as 12 times higher than the lowest value. These dramatic fluctuations in the absolute concentration of dopa in plasma had a major influence on the relative dopa concentrations (calculated as the ratio dopa/sum of LNAA) as the fluctuations in the concentrations of LNAA in plasma were much less pronounced. Consequently, the absolute and the relative concentrations of dopa in plasma were highly parallelled. In four of the five patients "on"-periods began within one hour after a peak in the concentration of dopa in plasma and in the fifth patient five out of seven "on"-periods were preceded by a rise in plasma dopa concentration within the same time interval. From the present data it could be concluded that the "on-off" phenomenon in Parkinson's disease, at least partly, is due to oscillations in the concentration of dopa in plasma. A reduction in the variations of the concentration of dopa in plasma seems to be necessary to overcome the "on-off" problem. The introduction of a slow release preparation of dopa is therefore urgently warranted. The concentration of LNAA in plasma must, however, also be considered in this context.
TL;DR: The results from this investigation clearly indicate a caudal to rostral maturational gradient in the development of endogenous GABA concentrations as well as synthesis capacity.
Abstract: Various biochemical characteristics of the developing GABA system was studied in rats from 1 to 60 days of age. Endogenous GABA concentrations were high in the limbic system, midbrain, brain stem and spinal cord at birth. Until 7 days of postnatal age, GABA concentrations generally decreased, thereafter an increase was seen and at 60 days of age the GABA concentrations exceeded those found in the neonate except for the spinal cord regions. After GABA-T inhibition with AOAA, GABA concentrations increased in all brain regions, however considerably more marked in the 28 days old rats compared to the 4 days old animals. Turnover rate of GABA was estimated by investigating the rate of disappearance of GABA after GAD inhibition with 3-MPA. Calculated turnover time of whole brain GABA was 34.1 min in the 4 days old rats and 19.9 min in the 28 days old animals. The results from this investigation clearly indicate a caudal to rostral maturational gradient in the development of endogenous GABA concentrations as well as synthesis capacity. Furthermore, turnover rate of total whole brain GABA but probably not of GABA in the neuronal pool is retarded in the 4 days old rats compared to the adolscent animals.
TL;DR: β-endorphin-like immunoreactivity in plasma has been measured by use of a highly sensitive and relatively specific radioimmunoassay and it is found that high-dosage diazepam treatment induces a slight reduction of plasmaβ-ELI, a finding which is attributed to antistress effect ofdiazepam.
Abstract: In 14 schizophrenic patients, treated with neuroleptic drugs, and in 7 patients, treated with high-dosage diazepam, beta-endorphin-like immunoreactivity in plasma has been measured by use of a highly sensitive and relatively specific radioimmunoassay. Neuroleptic treatment induced a significant increase of beta-endorphin-like immunoreactivity (beta-ELI). The pharmacological and clinical implications of this finding are discussed. High-dosage diazepam treatment induces a slight reduction of plasma beta-ELI, a finding which is attributed to antistress effect of diazepam.
TL;DR: It was found that changes in pineal gland volume could not be correlated with the light/dark phases; instead, a rhythm with a two-day period was encountered.
Abstract: Previous studies aimed at elucidating day/night changes of pineal gland size and pinealocyte nuclear volume have yielded contradictory results The aim of the present investigation was to examine the above parameters over a period of 10 successive days, at 6-hour intervals under a lighting regimen of LD 12∶12 (7 am to 7 pm) It was found that changes in pineal gland volume could not be correlated with the light/dark phases; instead, a rhythm with a two-day period was encountered Pinealocyte nuclear volume, by contrast, showed clear circadian changes, exhibiting troughs during photophase and peaks during scotophase
TL;DR: Intrapineal stimulation and recording in the guinea-pig indicate functional connections between anterior and posterior parts of the pineal organ and that information can be conducted in both directions of the Pineal axis.
Abstract: The possible influence of central nervous structures on the electrical activity of single pineal cells was investigated in rat and guinea-pig.
TL;DR: Levels of PEA in the rat brain and the effects of various monoamine oxidase (MAO) inhibitors thereon have been determined and the lowest and highest values found were 0.4 and 12.5 ng/g tissue, respectively.
Abstract: A highly specific and sensitive method for the determination ofβ-phenylethylamine (PEA) in biological material is presented. It involves prepurification of the extracts on Sep-Pak C18 cartridges, derivatization with heptafluorobutyric acid anhydride, gas chromatography on 50 m capillary columns and quantification by chemical ionization mass spectrometry. Using this method, levels of PEA in the rat brain and the effects of various monoamine oxidase (MAO) inhibitors thereon have been determined. PEA control levels were found to vary considerably: the lowest and highest values found were 0.4 and 12.5 ng/g tissue (n=25). Within one and the same control group, the variation was somewhat smaller. The preferential or specific inhibitors of MAO A, amiflamine, cimoxatone, CGP11305 A, moclobemide and toloxatone did not alter rat brain PEA even at high doses. In contrast, the preferential inhibitors of MAO B, deprenil, pargyline and MD 780236, as well as the nonselective agent tranylcypromine, caused strong (up to about 60-fold) increases. The threshold doses corresponded to those which caused about an 80 % inhibition of MAO B as measuredex vivo. The method was also used to determine the concentration of PEA in human CSF (mean 17.3±3.3 ng/ml, range 3–45 ng/ml, n=15) and urine (males: mean 35±5μg/g creatinine, range 3.8–219μg/g, 78 control days of a total of 12 subjects; females: mean 35±6μg/g creat., range 2.7–266μg/g, 55 control days of a total of 8 subjects).
TL;DR: The levels of 5-HIAA and free and total 5-hydroxytryptophol in human and rat brain regions and plasma were determined by a specific capillary column gas chromatographic-mass spectrometric method.
Abstract: The levels of 5-hydroxyindoleacetic acid (5-HIAA) and free and total 5-hydroxytryptophol (5-HTOL) in human and rat brain regions and plasma were determined by a specific capillary column gas chromatographic-mass spectrometric method. The human brains were obtained 2–3 hourspost mortem, and the levels of 5-HIAA were in the range of 0.48–31.3 nmoles/g in the regions investigated. The levels of free and total 5-HTOL were 10.9–387 pmoles/g and 14.5–821 pmoles/g, respectively. The ratio of total 5-HTOL to 5-HIAA was in the range of 0.6–5.5%. In human plasma the levels of free and total 5-HTOL were 0.9±0.3 and 2.9±0.8 pmoles/ ml±S.E.M., respectively. In regions of rat brain, the 5-HIAA levels ranged from 0.37–2.84 nmoles/g. Free and total 5-HTOL were in the range of 11.4–56.1 and 16.2–77.1 pmoles/g, respectively. The ratio of total 5-HTOL and 5-HIAA ranged from 2.3–5.1%. Higher levels of 5-HIAA and 5-HTOL occurred in the rat pineal gland. In rat plasma the levels of free and total 5-HTOL were 1.34±0.06 and 21.6±1.6 pmoles/ml±S.E.M., respectively.
TL;DR: The findings show that baclofen enantiomers have direct actions on stereoselective spinal mechanisms and that spinalization fails to alter the stereoselectedivity of spinal mechanisms towards the enantiomer.
Abstract: Spinal rats and rats with an intact neuraxis received an intrathecal injection of an enantiomer of baclofen. TheR-enantiomer was 100–1000 times more potent than its antipode in inhibiting the tail-flick reflex, both in intact rats and in spinal rats. Spinalization enhanced the inhibitory effects of both enantiomers without altering their dose-response relations. The findings show that baclofen enantiomers have direct actions on stereoselective spinal mechanisms and that spinalization fails to alter the stereoselectivity of spinal mechanisms towards the enantiomers.
TL;DR: 144 depressed in-patients were rated by means of the Comprehensive Psychopathological Rating Scale (CPRS) and platelet monoamine oxidase (MAO) was determined and it was hypothesized that patients with depressive disorders with pain as a symptom may have more pronounced disturbances in the serotinergic systems than patients without pain asA symptom.
Abstract: 144 depressed in-patients were rated by means of the Comprehensive Psychopathological Rating Scale (CPRS) and platelet monoamine oxidase (MAO) was determined. 49 per cent of the patients were found to have pain as a symptom, and 21 per cent were found to have more severe pain. The patients with more severe pain were found to have lower platelet MAO activity than the patients without pain or with slight pain. As platelet MAO activity may reflect the turn-over in the serotinergic systems in CNS it is hypothesized that patients with depressive disorders with pain as a symptom may have more pronounced disturbances in the serotinergic systems than patients without pain as a symptom.
TL;DR: The hypothesis was forwarded that satietin may play the role of a rate limiting blood-borne satiety signal in the negative feedback of food intake,i.e. serving as the essential chemical link connecting the gastrointestinal tract and the brain in the regulation of feeding.
Abstract: Satietin, a 50,000 dalton anorectic glycoprotein was isolated from human serum. Its isoelectric point is 7.0. It contains 14–15% amino acids and 70–75% carbohydrates. Its biological activity survives digestion with proteases and boiling. Satietin is a highly potent anorectic substance. The intracerebro-ventricular administration of 10–20μg satietin suppresses food intake in rats during the first day of feeding after deprivation of food for 96 hours to half of the amount eaten by untreated controls (ID50). The onset of the effect can be detected within 30 minutes, the peak effect is reached within an hour. The effect lasts 24–30 hours. Satietin acts both at intravenous and subcutaneous administration (ID50=0.5–0.75 mg/kg) in rats deprived of food for 96 hours. The peak effect is reached within an hour and lasts over 24 hours. In contrast to the anorectic drugs in clinical use and to the endogenous anorectic substances (like cholecystokinin and calcitonin) satietin proved to be highly selective in suppressing food intake. Considering that satietin is widely distributed in the world of vertebrates, its concentration in the blood is amazingly high, its site of effect is in the central nervous system and it induces satiety without having any other detectable central or peripheral effect, the hypothesis was forwarded that satietin may play the role of a rate limiting blood-borne satiety signal in the negative feedback of food intake,i.e. serving as the essential chemical link connecting the gastrointestinal tract and the brain in the regulation of feeding.
TL;DR: Dopamine receptors were localized autoradiographically in the rat spinal cord afterin vitro labelling using3H-N-propylnorapomorphine (NPA) and is compatible with a role for spinal cord dopamine in the processing of sensory information.
Abstract: Dopamine receptors were localized autoradiographically in the rat spinal cord afterin vitro labelling using3H-N-propylnorapomorphine (NPA). The highest densities of3H-NPA binding sites were found in the substantia gelatinosa and in a zone of the grey matter immediately ventral to the dorsal corticospinal tract. Other areas of the grey matter presented only moderate or low receptor densities while no3H-NPA binding sites could be found in the white matter. The localization of3H-NPA binding sites is compatible with a role for spinal cord dopamine in the processing of sensory information.
TL;DR: It is suggested that REM rebound phenomena produced by sleep deprivation in a Parkinson's disease patient are suppressed by the effect of the dopaminergic agent Pergolide.
Abstract: A 71 year old retired printer developed idiopathic Parkinson's disease over a period of 3 years On account of his worsening condition he was admitted to hospital Following the interruption of his medication the patient developed an akinetic crisis A 48 hour polysomnogram recording, repeated five times during hospitalization, showed severe sleep deprivation Treatment with Pergolide alone was then started; and sleep monitoring showed suppression of REM rebound, REM only appearing when the dose of the drug was reduced It is suggested that REM rebound phenomena produced by sleep deprivation in a Parkinson's disease patient are suppressed by the effect of the dopaminergic agent Pergolide
TL;DR: The sensitivity of hippocampal pyramidal neurons to the depressant action of serotonin was studied in hippocampal slices obtained from rats treated repetitively with clomipramine, and a moderate, non-significant reduction in sensitivity was observed with clorgyline.
Abstract: The sensitivity of hippocampal pyramidal neurons to the depressant action of serotonin was studied in hippocampal slices obtained from rats treated repetitively with clomipramine (10 mg/kg i.p.; 10 days or 4 weeks), with clorgyline (0.3 mg/kg s.c.; 10 days) or with the vehicle. Whereas clorgyline produced a very pronounced subsensitivity to serotonin, a moderate, non-significant reduction in sensitivity was observed with clomipramine. These electrophysiological findings are consistent with previous biochemical studies.
TL;DR: The predominant localization of the SOM-like immunoreactive neurons in the two enteric plexuses of the ileum was the most pronounced regional difference in the distribution pattern of the peptides.
Abstract: The localization of substance P-(SP-), methionine-enkephalin (met-Enk-) and somatostatin (SOM-)like immunoreactivity was studied in the cat pyloric sphincter, ileum, ileocecal sphincter and proximal colon. The enteric plexuses in all regions examined contained SP-, met-Enk- and SOM-like immunoreactive varicose nerve fibres. A large number of especially SP- and met-Enk-containing varicosities were often seen to encircle the nerve cell bodies and processes in the two ganglionic plexuses. The SOM-like immunoreactive perikarya were the only peptide-containing nerve cells, preferentially located in the submucous ganglia. The predominant localization of the SOM-like immunoreactive neurons in the two enteric plexuses of the ileum was the most pronounced regional difference in the distribution pattern of the peptides. Among the layers of the cat intestinal wall the circular muscle contained the most peptide-immunoreactive fibres in contrast to the longitudinal muscle. Evidence was obtained for the occurrence of single peptide-immunoreactive varicose nerve fibres in muscularis mucosae as well as around the glands and the blood vessels. Immunoreactive endocrine cells occurred mainly in the ileum mucosa.
TL;DR: Evidence is provided for the ability of the 3-MPA treatment used, to prevent the postmortem increase of not only cerebral, but also oviductal and ovarian GABA levels, and this procedure proved to be inadequate for fixation of GABA concentration in the kidney.
Abstract: The postmortem alteration of gamma-aminobutyric acid (GABA) levels was examined in the rat brain, kidney, ovary and oviduct up to 30 minutes after decapitation. GABA concentrations progressively increased with time in each organ. At 30 minutes, the following elevations were found in percent: brain 65, kidney 75, ovary 38 and oviduct 32. Pretreatment with 3-mercapto-propionic acid (3-MPA, 1.2 mmol/kg i.v.), 2.5 minutes prior to killing, completely prevented the postmortem increase of GABA levels in the brain, the ovary and the oviduct, but only slightly reduced the elevation of renal GABA content. In ex vivo experiments, the same treatment reduced with about 50 percent the activity of L-glutamate decarboxylase (GAD) in the brain and the oviduct, but failed to influence the enzyme activity in the kidney. In vitro, 3-MPA was far more potent in inhibiting cerebral and tubal than renal GAD. The present findings provide evidence for the ability of the 3-MPA treatment used, to prevent the postmortem increase of not only cerebral, but also oviductal and ovarian GABA levels. This procedure, however, proved to be inadequate for fixation of GABA concentration in the kidney.