Disappearance Of Catecholamines Research Articles

Effects of Combined Pre‐ and Postnatal Treatment with Nicotine on Hypothalamic Catecholamine Nerve Terminal Systems and Neuroendocrine Function in the 4‐Week Old and Adult Male and Female Diestrous Rat

Abstract Male and female Sprague-Dawley rats were treated with nicotine during the prenatal period and the first three postnatal weeks (the pregnant and lactating rats were given nicotine hydrogen (+) tartrate (165 mg/l) in the tap water). Catecholamine fluorescence was evaluated using quantitative histofluorometry on brain sections treated according to Falck-Hillarp methodology. In order to evaluate catecholamine utilization in discrete hypothalamic catecholamine nerve terminal networks, the alphaMT- (alpha-methyl-(+/-)-p-tyrosine methyl ester) induced catecholamine disappearance was studied 2 h following the tyrosine hydroxylase inhibition. The body weight was reduced in both the male and female rats from 3 weeks of age until 9 weeks of age following pre- and postnatal treatment with nicotine. Following one week of withdrawal from pre- and postnatal treatment with nicotine, an increased catecholamine utilization was observed in the medial and lateral palisade zones of the median eminence mainly in the female rat. In the female rat, reduced prolactin serum levels were found both in the presence and absence of alphaMT treatment as well as reduced luteinizing hormone concentration in the presence of alphaMT treatment. At 6 months of age indications of a maintained, weak activation of the catecholamine nerve terminal systems in the medial palisade zones of the median eminence were observed in male rats pre- and postnatally treated with nicotine. Furthermore, increased noradrenaline levels were found in the paraventricular hypothalamic nucleus. An increase in serum luteinizing hormone levels was also found in these rats. In the 7-month old diestrous rat, maintained marked increases in catecholamine utilization in the medial and lateral palisade zones of the median eminence were found following treatment with nicotine during the pre- and postnatal period. A significant reduction of nigral dopamine stores was also demonstrated. The serum levels of thyroid stimulating hormone, prolactin and luteinizing hormone were unchanged in these rats both in the presence and absence of tyrosine hydroxylase inhibition. Finally, pre- and postnatal treatment with nicotine did not alter [(3)H]nicotine binding (quantitative receptor autoradiography) in cortical, striatal and thalamic areas of the adult diestrous rat. The results demonstrate that pre- and postnatal treatment with nicotine in the drinking water produces permanent activations of the catecholamine nerve terminal networks of the external layer of the median eminence mainly in the female rat. These changes appear to be associated with reduced serum prolactin levels in the 4-week old female rat. Sex-specific changes occur in discrete noradrenaline nerve terminal systems. The observed changes may have functional consequences for neuroendocrine regulation and for the regulation of food and water intake as well as sex-specific responses to stress in the male versus the female rat. Nicotine-induced disturbances in brain cell replication and differentiation may underlie the permanent alteration found in discrete catecholamine neuron systems after pre- and postnatal exposure to this drug.

Oxytocin affects utilization of noradrenaline in distinct limbic-forebrain regions of the rat brain

The effects of oxytocin, administered intracerebroventricularly in doses of 1, 10, 100 and 1000 pmol, were studied on the disappearance of catecholamines induced by α-methyl- p-tyrosine in microdissected nuclei of the rat brain. Oxytocin dose-dependently decreased the utilization of noradrenaline in the lateral and medial septal nuclei and anterior hypothalamic area, whereas an enhanced utilization was observed in the nucleus supraopticus. Tendency towards a change in utilization of noradrenaline was found in the dorsal septal nucleus and the lateral amygdala. Utilization of dopamine was not significantly affected in any of the nuclei of the brain studied. Tendency towards a decrease in utilization of dopamine was observed in the nucleus caudatus, globus pallidus and medial septal nucleus. It thus appears that oxytocin elicited changes in only a restricted number of brain nuclei. Interestingly, these nuclei contain cell bodies (nucleus supraopticus) and terminals (other nuclei) of the oxytocin system in the brain. Though the effects of oxytocin were not as widespread as those previously seen after administration of vasopressin, it is worthy of note that, in general, the effects of oxytocin were opposite to those seen after vasopressin. The opposite effecs of vasopressin and oxytocin on catecholamine metabolism could be related to the opposite effects of the two peptides on behaviour, neuroendocrine and autonomie regulation.

Pro-Leu-GlyNH 2 affects dopamine and noradrenaline utilization in rat limbic-forebrain nuclei

The effects of Pro-Leu-GlyNH 2 (PLG), administered i.c.v. in doses of 3.5, 35, 350 and 3500 pmol, were studied on the α-MPT-induced disappearance of catecholamines in microdissected rat brain nuclei. PLG, dose-dependently, increased dopamine disappearance in the nucleus caudatus and globus pallidus, whereas a decrease in dopamine disappearance was observed in the nucleus dorsomedialis. Noradrenaline disappearance was decreased in the medial septal nucleus, anterior hypothalamic area and lateral amygdala. A tendency towards an increase in noradrenaline disappearance was observed in the nucl. supraopticus. These data show that PLG has a central site of action. The effects of PLG on dopamine disappearance are comparable to those previously found with vasopressin, while the effects of PLG on noradrenaline utilization show a striking similarity with those previously obtained with oxytocin.

Monoamine neurotransmitter metabolism in microencephalic rat brain after prenatal methylazoxymethanol treatment

Administration of methylazoxymethanol (MAM) in the fetal stage leads to forebrain microencephaly with a severe atrophy in cerebral cortex, striatum, and hippocampus. The concentration of endogenous monoamines was markedly increased in the atrophie regions while total amount was largely unchanged. Striatal dopamine and cortical noradrenaline nerve terminals from MAM treated animals showed unaltered sedimentation properties in a sucrose density gradient and were estimated to have normal transmitter levels. γ-Butyrolactone induced increase in dopamine levels and its counteraction by apomorphine was essentially unaltered after MAM. These data give further support for the view that the monoamine nerve terminal fields develop to their normal size in the atrophie regions leading to a hyperinnervation. Analysis of monoamine metabolite levels, increase of monoamines after monoamine oxidase inhibition, and disappearance of catecholamines after tyrosine hydroxylase inhibition were conducted to obtain information on monoamine turnover. The results indicated an essentially unaltered, or a small reduction of, monoamine turnover in the atrophie regions when calculated per monoamine nerve terminal, while increased when calculated per unit weight of the tissue.

Effects of oxytocin, des-glycinamide-oxytocin and anti-oxytocin serum on the α-MPT-induced disappearance of catecholamines in the rat brain

Oxytocin (OXT) attenuates memory processes and endogenous OXT might be regarded as an amnesic neuropeptide. In this study, the mode of action of OXT on brain catecholaminergic neurotransmission has been analyzed. Peripheral injection of OXT facilitated the α-MPT-induced disappearance of noradrenaline (NA) in the mesencephalon. Dopamine (DA) disappearance was inhibited in the mesencephalon and facilitated in the striatum. The accelerated striatal DA disappearance was not observed if the peptide was given together with α-MPT, but only if OXT was injected after α-MPT treatment. Intraventricular injection of OXT or des-glycinamide-oxytocin (DG-OXT) caused a decrease in the DA disappearance in the mesencephalon, whereas central administration of anti-oxytocin serum (anti-OXT) accelerated the DA disappearance in the same region. The data raise the possibility that DA utilization in the mesencephalon may be correlated with the influence of OXT on CNS processes.

Adrenergic nerves and mast cells after skin freezing. A hypothesis based on fluorescence microscope observations in the rat

After freezing and thawing of rat skin, degranulation and disappearance of mast cell fluorescence became apparent in the skin up to 1 h after thawing. Gradual disappearance of catecholamines from the adrenergic nerves of the injured area occurred during the 1st 24 h. Both mast cells and adrenergic nerves may play a role in tissue destruction after freezing injury.

Selective blockade of brain alpha 2-autoreceptors by yohimbine: effects on motor activity and on turnover of noradrenaline and dopamine.

The motor activity of groups of three mice was increased by yohimbine at doses up to 3 mg/kg intraperitoneally. The turnover of dopamine and noradrenaline in the mouse brain, as assessed by the disappearance of catecholamines following treatment with the tyrosine hydroxylase inhibitor alpha-methyltyrosine, was accelerated by yohimbine with a peak effect after 10 mg/kg intraperitoneally. Prazosin (3 mg/kg i.p.) completely antagonized the stimulatory effect of yohimbine on motor activity and on dopamine turnover but it somewhat potentiated the stimulatory effect on the turnover of noradrenaline. Amphetamine reversed the prazosin-induced hypomotility, indicating that prazosin can selectively block postsynaptic alpha 1-receptors. Yohimbine did not stimulate motor activity following 10 mg/kg and it retarded the turnover of dopamine following 30 mg/kg. These actions might be due to blockade of postsynaptic alpha-receptors by yohimbine. The data indicate that yohimbine at low doses stimulates motor activity and dopamine turnover by selectively blocking alpha 2-autoreceptors leading to increased release of noradrenaline and subsequent activation of post-synaptic alpha 1-receptors.

Effects of CRF-like heptapeptide on catecholamine disappearance and serotonin accumulation in different brain areas of rats

The effects of intracerebroventricular administration of 1.0 ug of Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH /DC-9-39/ on the α-methyl-p-tyrosine /α-MPT/ -induced catecholamine disappearance and pargyline-induced serotonin accumulation in the hypothalamus, mesencephalon, septum, amygdala, cortex and striatum were studied. The dopamine disappearance was reduced in the hypothalamus and striatum, while it was increased in the septum. The serotonin accumulation was decreased in the hypothalamus, amygdala and cortex, but increased in the septum. The data indicate that this heptapeptide is able to modify the activities of the brain catecholaminergic and serotoninergic systems.

Effect of des-tyr 1-γ-endorphin and des-tyr 1-α-endorphin on α-MPT-induced catecholamine disappearance in rat brain nuclei: A dose-response study

The effect of des-Tyr 1-γ-endorphin (ß-LPH 62–77, DTγE) and des-Tyr 1-α-endorphin (ß-LPH 62–76, DTαE), administered intracerebroventricularly (icv) in doses of 0.01, 0.1, 1 and 10 μg, was studied on the α-methyl-p-tyrosine- (α-MPT) induced disappearance of catecholamines in a number of microdissected rat brain regions, which were selected on the basis of the neuroanatomy of the dopamine systems in the brain and of previous observations. A dose-dependent increase in the disappearance of dopamine in α-MPT-pretreated rats was observed following icv administration of DTγE in the nucleus interstitialis striae terminalis, the paraventricular nucleus, the anterior hypothalamic nucleus and the zona incerta. In these same brain regions a decrease in the α-MPT-induced disappearance of dopamine was found following the administration of DTαE, but only after doses of 0.01, 0.1 and 1 μg. In none of these regions were effects observed after 10 μg of DTαE. No effects were seen on dopamine utilization in the nucleus accumbens, caudate nucleus and median eminence after any of the doses of DTγE or DTαE. The α-MPT-induced disappearance of noradrenaline was significantly enhanced in the anterior hypothalamic nucleus of rats treated with DTγE. It is concluded that DTγE and DTγE induce opposite changes in the utilization of dopamine selectively in brain regions which are predominantly innervated byneurons belonging to the intradiencephalic dopamine systems.

Effects of β-/Tyr 9/melanotropin-/9–18/ decapeptide on catecholamine disappearance and serotonin accumulation in discrete brain regions of rats

The effects of intracerebroventricular administration of a 1.0 ug dose of Tyr-Phe-Arg-Trp-Gly-Ser-Pro-Pro-Lys-Asp /DC-11-18/ on the α-methyl-p-tyrosine / α-MPT/-induced catecholamine disappearance and the pargyline-induced serotonin accumulation in the hypothalmus, mesencephalon, amygdala, septum, cortex and striatum were studied. The dopamine disappearance was facilitated in the septum, while it was impeded in the striatum. The norepinephrine disappearance was lowered in the amygdala. The serotonin accumulation was inhibited in the hypothalamus and enhanced in the septum. The data indicate that this decapeptide is able to modify the activities of catecholamines and serotonin in different brain regions.

Dose-related effect of the oxytocin fragment (prolyl-leucyl-glycinamide) on α-MPT-induced catecholamine disappearance and serotonin level in rat brain

Graded doses of Pro-Leu-Gly-NH(2) (3.5 x 10(?12), 3.5 x 10(?11), 3.5 x 10(?10) or 3.5 x 10(?9) mol) were administered into the lateral cerebral ventricle of rats. The noradrenaline level of the dorsal hippocampus was increased 30 min after a dose of 3.5 x 10(?10) mol Pro-Leu-Gly-NH(2). The dopamine level was increased in the dorsal hippocampus and in the striatum. The serotonin level was increased in the hypothalamus, in the striatum and decreased in the dorsal hippocampus. The catecholamine disappearance following 350 mg/kg of ?-methyl-p-tyrosine indicated an accelerated dopamine disappearance in the striatum for each dose studied, while the hypothalamic noradrenaline disappearance was inhibited by a dose of 3.5 x 10(?11) mol of Pro-Leu-Gly-NH(2). The data indicate that Pro-Leu-Gly-NH(2) induces dose and region-dependent changes in the cerebral monoamine metabolism. The striatal dopamine and hypothalamic serotonin metabolism appeared to be the most sensitive for intraventricular Pro-Leu-Gly-NH(2).

Effects of α-endorphin, β-endorphin and (des-tyr 1)-γ-endorphin on α-MPT-induced catecholamine disappearance in discrete regions of the rat brain

Following the intracerebroventricular administration of α-endorphin, β-endorphin and (des-tyrosine 1 )-γ-endorphin in a dose of 100 ng, the α-MPT-induced catecholamine disappearance was found to be altered in discrete regions of the rat brain. In the regions in which α-endorphin exerted an effect, it without exception caused a decrease in catecholamine disappearance. Thus, in rats treated with α-endorphin the disappearance of noradrenaline was decreased in the medial septal nucleus, dorsomedial nucleus, central amygdaloid nucleus, subiculum, the ventral part of the nucleus reticularis medullae oblongatae and the A1 region, and that of dopamine in the caudate nucleus, globus pallidus, medial septal nucleus, nucleus interstitialis striae terminalis, paraventricular nucleus, zona incerta and central amygdaloids nucleus. β-endorphin was found to decrease noradrenaline disappearance in the ventral part of the nucleus reticularis medullae oblongatae, dopamine disappearance in the lateral septal nucleus and the disappearance of both amines in the rostral part of the nucleus tractus solitarii. Dopamine disappearance was increased in the medial septal nucleus and the zona incerta following β-endorphin treatment. Following treatment with (des-tyrosine 1 )-γ-endorphin, noradrenaline disappearance was enhanced in the anterior hypothalamic nucleus, whereas dopamine disappearance was increased in the paraventricular nucleus, the zona incerta and the rostral part of the nucleus tractus solitarii. In addition to this the latter peptide also caused a decreased noradrenaline disappearance in the periventricular thalamus and the A7 region. The results fit well with the suggestion that endorphins act as modulators of catecholamine neurotransmission in particular brain regions. The pattern of effects of the endorphins differ from that previously observed following intracerebroventricular administration of methionine-enkephalin. This is in keeping with the notion that the enkephalin containing network in the brain and that containing β-LPH represent two independent systems with distinct differences in their projections to various brain regions.

Differences in regional brain catecholamine metabolism after a decrease in blood pressure.

Abstract Using a sensitive radiometric assay for determination of catecholamines, the α-methyl-para-tyrosine-induced catecholamine disappearance was studied in discrete brain regions of rats after acute hypotension. The decrease in blood pressure was induced either by controlled haemorrhage or by the administration of guanethidine. In both cases an increase of the α-methyl-para-tyrosine-induced noradrenaline disappearance was observed in the nucleus commissuralis and the A1-region in the medulla oblongata. In the paraventricular nucleus the disappearance of noradrenaline as well as that of adrenaline was enhanced. The results are in support for the involvement of catecholamines in particular brain regions in the regulation of blood pressure.

Prolyl-leucyl-glycinamide (PLG); regional effects on α-MPT-induced catecholamine disappearance in rat brain

Prolyl-leucyl-glycinamide (PLG); regional effects on α-MPT-induced catecholamine disappearance in rat brain

Behavioral and electrocortical activity in rats after neonatal intraventricular 6-hydroxydopamine administration

Intraventricular injections of 6-hydroxydopamine (6-OHDA) to newborn rats resulted in a nearly complete disappearance of catecholamines in brain regions containing nerve terminals. In the hypothalamus, however, dopamine was only decreased to 60% of control levels. The exploratory (rearing and crossing) and some of the automatic type behavioral activities (grooming, chewing and gnawing), the duration of neocortical synchronization and hippocampal theta frequency were measured during light and dark periods in adulthood. Decreased exploratory and increased automatic behavioral activities were found in both light and dark periods and a high incidence of neocorticol synchronization and a lowered hippocampal theta frequency in the light phase when the animals were repeatedly subjected to a strange environment. The light-dark rhythmicity of exploratory and hippocampal activity remained intact in the 6-OHDA treated rats. Furthermore, the diurnal periodicity of general motor activity was also normal. It was concluded that contrary to the active involvement of prepontine catecholamine structures in the behavioral and electrocortical responses in a novel situation, their role in controlling the light-dark rhythmical processes may not be essential.

Effect of single and repeated administration of clozapine on the metabolism of dopamine and noradrenaline in the brain of the rat

• Clozapine is a novel antischizophrenic drug that lacks extrapyramidal side effects in man and is not cataleptogenic in the rat. Its action on the synthesis and disappearance of catecholamines in the rat brain was compared with that of four typical (i.e. cataleptogenic) neuroleptics, haloperidol, chlorpromazine, loxapine, and the 2-chloro isomer of clozapine, HF-2046. Clozapine enhances the dopamine content of the striatum while the typical neuroleptics always decrease the dopamine level, probably as a consequence of turnover stimulation. Upon repeated administration, the dopamine-enhancing effect of clozapine becomes more pronounced while the dopamine turnover stimulation caused by typical neuroleptics diminishes. At high doses, clozapine also stimulates disappearance of dopamine as shown by the accumulation of homovanillic acid. This effect, however, does not decrease upon repeated administration as it does with typical neuroleptics. Single or repeated doses of clozapine do not interfere with dopamine turnover stimulation induced by the administration of haloperidol or loxapine. It is therefore thought that clozapine stimulates the synthesis of striatal dopamine much more strongly than its disappearance, and that it does not primarily block dopamine receptors as typical neuroleptics are thought to do. • Clozapine stimulates the turnover of NA in the brain stem of the rat, but this effect is markedly diminished upon repeated administration. Thus, it appears that clozapine acts on the NA system of brain stem in a way similar to that of the typical neuroleptics.

Regional Disappearance of Catecholamines Formed from 14C‐Tyrosine in Rat Brain: Effect of Synthesis Inhibitors and of Chlorpromazine

The disappearance of labelled catecholamines formed in vivo from 14C‐tyrosine in the whole rat brain and in different regions of the rat brain has been studied. The elimination of the labelled amines from the brain followed first order kinetics between one and ten hours after 14C‐tyrosine administration. The half‐lives were 2.9 hours for 14C‐dopamine and 5.3 hours for 14C‐noradrenaline. The rate of disappearance of 14C‐dopamine was highest in the cerebral cortex and striatum and lowest in the cerebellum. The rate of disappearance of 14C‐noradrenaline was highest in the cerebellum and lowest in the diencephalon. The use of the disappearance of labelled catecholamines as a measure of turnover of endogenous amines is discussed on the basis of results obtained with the tyrosine hydroxylase inhibitor H 44/68 and the dopamine‐β‐hydroxylase inhibitor FLA 63. It is suggested that FLA 63 accelerates noradrenaline turnover and also affects dopamine neurons in the brain. In accordance with previous studies on the accumulation of labelled catecholamines formed from 14C‐tyrosine in rat brain regions, chlorpromazine accelerated the disappearance of 14C‐dopamine in the striatum but had no significant effect in the other regions. The disappearance of 14C‐noradrenaline was not influenced by chlorpromazine in any of the regions studied. The results support the view that chlorpromazine accelerates dopamine turnover in the rat striatum.

Effect of brain lesions and chlorpromazine on accumulation and disappearance of catecholamines formed in vivo from 14 C-tyrosine.

AbstractRats were subjected to a unilateral stereotaxic lesion at the level of the mesencephalic‐hypothalamic junction where the nigro‐striatal dopamine (DA) pathway is known to pass. Between 6 and 18 h after the lesion the level of DA in the striatum on the same side was increased by about 50 per cent. Between 18 and 48 h after the lesion the content of DA declined to 15 per cent of that of the contralateral striatum and stayed at this low level during the following 6 days. The content of noradrenaline (NA) tended to be increased 24 h after the lesion but no change was found on the following days. The accumulation and disappearance of 14C‐DA formed from 14C‐tyrosine in the striatum 12–24 h after the nigral lesion were decreased on the lesion side in comparison with the contralateral side. The accumulation and disappearance of 14C‐NA did not differ between the 2 sides. Chlorpromazine accelerated both accumulation and disappearance of 14C‐DA in the striatum on the side contralateral to the lesion but not in the striatum of the lesion side. In animals with a unilateral lesion above the DA pathway, in the posterior thalamus, chlorpromazine accelerated the accumulation of 14C‐DA on both sides. The accumulation of 14C‐XA in the striatum was increased by chlorpromazine on the intact side following both types of lesions. The disappearance of 14C‐NA, however, was not influenced by the drug. The results are taken as evidence that chlorpromazine accelerates DA turnover in the striatum by activating the nerve impulse flow in the nigro‐striatal DA pathway.

Effect of -adrenoceptor blocking agents on poststimulatory atrial flutter in the dog, with observations on the participation of adrenergic mechanisms in this experimental arrhythmia.

1. Four beta-adrenoceptor antagonists, viz. (+/-) propranolol (0.5 mg/kg), (-) alprenolol (0.25 mg/kg), practolol (5 mg/kg) and USVC 6524 (20 mug/kg), were tested for their effects on atrial flutter produced by electrical stimulation of the right atrium around the crushed inter-venae-caval bridge in anaesthetized dogs.2. All the drugs reduced atrial and ventricular rates; this was followed by the abrupt termination of flutter and restoration to normal sinus rhythm.3. Since all the drugs (including practolol, which is devoid of local anaesthetic activity) were given in doses just sufficient to block beta-adrenoceptors, it indicated that beta-adrenoceptor blockade was responsible for their antiarrhythmic property in this test procedure.4. Further evidences in support of participation of the sympathetic nervous system in poststimulatory flutter were: (i) flutter could not be produced in nine out of ten dogs whose catecholamine stores were depleted by pretreatment with reserpine; (ii) infusion of adrenaline in these animals resulted in the production of flutter; (iii) duration of flutter after termination of exposure to adrenaline was a few minutes, which is similar to the brief time previously reported to be taken for the disappearance of catecholamines from the hearts of reserpinized animals.5. The clinical significance of the above findings is discussed.

Further studies on the accumulation and disappearance of catecholamines formed from tyrosine- 14C in mouse brain. Effect of some phenothiazine analogues

Tyrosine- 14C was administered to conscious mice by i.v. injection or constant rate i.v. infusion. The time courses for accumulation and disappearance of tyrosine- 14C, dopamine- 14C and noradrenaline- 14C in brain were determined. Significant amounts of adrenaline- 14C were not formed from the labelled precursor as shown by paper chromatography. Following labelling of the catecholamine stores in brain by i.v. injection of tyrosine- 14C the decline of 14C-catecholamine levels yielded linear semilog plots between 2 and 7 hr after precursor administration. The slope of the curves for 14C-catecholamine disappearance was not altered on treatment with the tyrosine hydroxylase inhibitor α-methyl-tyrosine. When tyrosine- 14C was administered by constant rate i.v. infusion the contents in brain of labelled dopamine and noradrenaline increased with time demonstrating that the rate of synthesis of labelled amines exceeded the rates of catabolism and release. The procedures were used to study the effects of promethazine, levomepromazine, chlorpromazine, perphenazine and chlorprothixene. The neuroleptic phenothiazine analogues, but not the non-neuroleptic promethazine, accelerated the disappearance rates of both dopamine- 14C and noradrenaline- 14C. The clinically, most potent neuroleptic seemed to accelerate dopamine- 14C disappearance somewhat more than noradrenaline- 14C disappearance. During infusion of tyrosine- 14C all neuroleptics accelerated the accumulation of dopamine- 14C more than that of noradrenaline- 14C. It is suggested that neuroleptic phenothiazine analogues accelerate turnover of both dopamine and noradrenaline. Neuroleptic properties seemed to be best correlated to an increased synthesis and turnover of dopamine. Sedative properties might be better correlated to an increased synthesis and turnover of noradrenaline.