The effect of adrenoblockers on the neurons of the lateral hypothalamus under the action of pentagastrin]

To test the hypothesis of interaction pentagastrin (PG) noradrenaline (NA) in central neurochemical mechanisms of food motivation, we studied the activity of single neurons in lateral hypothalamus (LH) after s.c. PG injection. Following PG injection microiontophoresis (MIF) of propranolol prazosin was made. PG-induced changes were similar to neuronal activity in rabbits LH after 24-hour food deprivation in 59%. Propranolol-induced changes were following firing pattern in the process of food uptake in 68%. Prazosin MIF induced firing pattern of neuronal activity of saturated rabbits in 60%.     

Relationship of the activity of cardiac cholinergic mechanisms to the state of the sympathetic innervation and its noradrenaline content in hypoxia]

Preliminary sympathectomia depletes acetylcholine (ACh) in the heart of rabbits under hypoxia. In these conditions the inhibitory action of ACh on the rat isolated heart is reduced under the noradrenaline content fall, while under increase it is potentiated. Under hypoxia noradrenaline increases concentration of potassium in the myocardium, thus stimulating ACh formation and activity. It is suggested that under deep hypoxia suppression of the sympathetic mechanisms causes functional isolation of the heart from nervous effects.     

Neuropeptides in the mechanisms of the activation of escape reactions induced by stimulation of the ventromedial hypothalamus during food motivation satiation

Influence of food intake on hypothalamically induced avoidance reactions have been studied in rabbits. It was shown that first contact with food and beginning of food intake accompany with activation of avoidance reactions. Central action of cholecystokinin-octapeptide, pentagastrin, beta-endorphin and naloxone on avoidance reactions of fed and fasted rabbits before and during food intake was investigated. It was found that injection of cholecystokinin and naloxone, which had a satiated effect, act on avoidance reactions similarly in fed and fasted rabbits. Beta-endorphin inhibits avoidance behavior, and only pentagastrin activates avoidance reactions of fasted but not fed rabbits. It is concerned that influence of feeding motivation may modulate avoidance behavior by participation of endogenous gastrin-like peptide release into the perineuronal area during contact of rabbits with food and beginning of its intake.     

Quantitation and immunohistochemistry of catecholamines in the posterior segment of the eye

Summary Dopamine, noradrenaline, and adrenaline were assayed with HPLC in the light adapted retinae of carp, frog, chicken, pigeon, rat, guinea-pig, rabbit, cat, pig and cow. Dopamine varied from 0.6 to 2.6 nmol/g wet weight and was not influenced by sympathectomy. The dopamine figures agree with previously published results. Noradrenaline concentrations varied from not detectable to 0.06 nmol/g wet weight in different species. Homolateral sympathectomy significantly decreased the noradrenaline figure in rabbits. There are no previous figures for noradrenaline for most of the species. Adrenaline was not detected in any species. Immunohistochemical analysis showed noradrenaline to be present in choroidal nerves, but noradrenaline immuno-reactivity was not seen in the retina (chicken, rat, guinea-pig, rabbit, cat, cow). It is concluded that dopamine is the major catecholamine in the retina. Noradrenaline was found present only in minute amounts in the assays, and much of its was likely to stem from sympathetic nerve fibres. The study did not demonstrate any noradrenergic neurons in the retina.     

Quantitation and immunohistochemistry of catecholamines in the posterior segment of the eye

Dopamine, noradrenaline, and adrenaline were assayed with HPLC in the light adapted retinae of carp, frog, chicken, pigeon, rat, guinea-pig, rabbit, cat, pig and cow. Dopamine varied from 0.6 to 2.6 nmol/g wet weight and was not influenced by sympathectomy. The dopamine figures agree with previously published results. Noradrenaline concentrations varied from not detectable to 0.06 nmol/g wet weight in different species. Homolateral sympathectomy significantly decreased the noradrenaline figure in rabbits. There are no previous figures for noradrenaline for most of the species. Adrenaline was not detected in any species. Immunohistochemical analysis showed noradrenaline to be present in choroidal nerves, but noradrenaline immuno-reactivity was not seen in the retina (chicken, rat, guinea-pig, rabbit, cat, cow). It is concluded that dopamine is the major catecholamine in the retina. Noradrenaline was found present only in minute amounts in the assays, and much of its was likely to stem from sympathetic nerve fibres. The study did not demonstrate any noradrenergic neurons in the retina.     

Catecholamine sulfates: end products or metabolic intermediates?

Dopamine-beta-hydroxylase catalyzes the beta-oxidation of dopamine to noradrenaline while phenylethanolamine-N-methyltransferase converts noradrenaline to adrenaline. Since catecholamine sulfates represent the predominant form of catecholamines in human tissues, we have studied the role of dopamine sulfate and noradrenaline sulfate as alternate substrates for dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase, respectively. Dopamine 3-sulfate, dopamine 4-sulfate and noradrenaline 3-sulfate were chemically synthesized and exhaustively purified by ion-exchange chromatography. Dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase were partially purified from human adrenals. Using tyramine as substrate, dopamine-beta-hydroxylase is slightly inhibited by dopamine 3-sulfate according to some irreversible or mixed mechanisms. When dopamine-beta-hydroxylase was incubated with dopamine 3-sulfate or dopamine 4-sulfate, we were not able to find any synthesis of either noradrenaline sulfate or free noradrenaline. Using phenylethanolamine as substrate, the enzymatic activity of phenylethanolamine-N-methyltransferase remains unchanged with addition of dopamine 3-sulfate, dopamine 4-sulfate or noradrenaline 3-sulfate. It was concluded that dopamine sulfate is not an alternate substrate for either dopamine-beta-hydroxylase or phenylethanolamine-N-methyltransferase nor is noradrenaline 3-sulfate an alternate substrate for phenylethanolamine-N-methyltransferase.     

The brain catecholamines during domestication of the silver fox Vulpes fulvus

Studies have been made on the content of catecholamines (noradrenaline and dopamine) as well as metabolites of dopamine (3,4-dihydroxyphenylacetic and homovanillic acids) in the brain structures of silver foxes which differ in their handling reactions. The level of noradrenaline was found to be significantly higher in the anterior hypothalamus of domesticated animals; no differences in noradrenaline content were found in the frontal cortex, hippocamp, posterior hypothalamus and midbrain in animals from aggressive and domesticated groups. Dopamine content was higher in the tuberculum olfactorium of domesticated animals, being lower in the striatum and n. accumbens. Metabolite level remained unaffected which is presumably due to changes in dopamine synthesis in the investigated structures. It was concluded that domestication of animals favours the specimens with an altered state of catecholaminergic system of the brain.     

Effect of neurotransplantation on the content of catecholamines in the rat brain structures after heavy craniocerebral trauma

It was found that heavy craniocerebral trauma (CCT) in rats results in a drop in the dopamine and noradrenaline content in the damaged cerebral hemisphere, striatum, and hypothalamus. Transplantation of embryonic neural tissue after CCT in rats favors restoration of the level of catecholamines. Thirty days after the transplantation, the level of noradrenaline and dopamine in damaged structures mentioned above becomes similar to that in intact animals, or exhibits a tendency to be restored.     

The effect of endogenous and exogenous GABA on the level and turnover of noradrenaline and dopamine in the rat brain

The effect of endogenous and exogenous GABA on the level and turnover of noradrenaline and dopamine in the rat brain. Acta Physiol. Pol., 1978, 29 (2): 117--121. GABA administered to the lateral ventricle of the rat brain (i.v.c.) in doses of 200 and 600 microgram decreased the level of noradrenaline and had no effect on dopamine level. A similar effect was obtained after raising the level of endogenous GABA in the brain by means of intraperitoneal hydroxylamine (Hx) in doses of 50 and 75 mg/kg. It was also observed that GABA given i.v.c. in a dose of 600 mg/kg reduces the turnover of dopamine in the brain.     

Stimulation of the locus coeruleus elicits noradrenaline and dopamine release in the medial prefrontal and parietal cortex

Our previous studies have suggested that dopamine and noradrenaline may be coreleased from noradrenergic nerve terminals in the cerebral cortex. To further clarify this issue, the effect of electrical stimulation of the locus coeruleus on extracellular noradrenaline, dopamine and DOPAC in the medial prefrontal cortex, parietal cortex and caudate nucleus was analysed by microdialysis in freely moving rats. Stimulation of the locus coeruleus for 20 min with evenly spaced pulses at 1 Hz failed to modify cortical catecholamines and DOPAC levels. Stimulation with bursts of pulses at 12 and 24 Hz increased, in a frequency-related manner, not only noradrenaline but also dopamine and DOPAC in the two cortices. In both cortices noradrenaline returned to baseline within 20 min of stimulation, irrespective of the stimulation frequency, whereas dopamine returned to normal within 20 and 60 min in the medial prefrontal cortex and within 60 and 80 min in the parietal cortex after 12 and 24 Hz stimulation, respectively. DOPAC remained elevated throughout the experimental period. Phasic stimulation of the locus coeruleus at 12 Hz increased noradrenaline in the caudate nucleus as in the cerebral cortices but was totally ineffective on dopamine and DOPAC. Tetrodotoxin perfusion into the medial prefrontal cortex dramatically reduced noradrenaline and dopamine levels and suppressed the effect of electrical stimulation. These results indicate that electrical stimulation-induced increase of dopamine is a nerve impulse exocytotic process and suggest that cortical dopamine and noradrenaline may be coreleased from noradrenergic terminals.     

Low selenium diet increases the dopamine turnover in prefrontal cortex of the rat

It has been proposed that interaction of catecholamines and indoleamines with free radicals may result in the formation of endogenous neurotoxins. In order to better understand the mechanisms involved in neurodegenerative disorders showing evidence of oxidative stress, we have studied the basal concentrations and the turnover rates of dopamine, noradrenaline, serotonin and their metabolites in the prefrontal cortex of rats that were fed on control or low selenium diets. Nutritional deficit of selenium decreases the brain antioxidant protection in experimental conditions by the decrease in glutathione peroxidase activity.

The dopamine and serotonin turnover increased and noradrenaline and 5-hydroxy-3-indoleacetic acid turnover decreased compared to experimental control animals. The increase of dopamine turnover in experimental rats was accompanied by an increase in tyrosine hydroxylase activity. These results suggest that the decrease of brain protection against oxidative damage could induce brain damage by disturbing the turnover rate of some monoamines.     

Shift of the catecholamine levels at stimulation of the hypothalamic emotiogenic zones

Using models of electrical self-stimulation of the positive emotiogenic zones and stimulation of the negative emotiogenic zones of the hypothalamus in rats, we demonstrated that both these stimulations increase the noradrenaline level in the frontal cortex. This shows a nonspecific nature of activation of the dorsal noradrenergic bundle, resulting from motivational excitation. When the frequency of self-stimulation reaction remained stable, activation of the dorsal noradrenergic bundle was moderate, and at decay of the above reaction it returned to the control level. Behavior connected with activation of the motor functions was characterized by an increase in the dopamine and noradrenaline levels in the caudate nucleus. In theglobus pallidum, the dopamine content changed only under conditions of stimulation of the negative emotiogenic zones: these were an increase in the reaction of active avoidance and a decrease in passive avoidance.     

The effect of 6-hydroxydopamine on the behavior of rats with differing resistance to stress exposure

The influences of 6-OHDA (150 mcg intraventricular, bilaterally) on the behaviour of Wistar rats with different resistance to sound-stress were studied. Reduction of reactivity, exploratory activity and learning deterioration after 6-OHDA administration were observed. The behavioural disturbances were more demonstrative in stress-resistant rats. Biochemical estimations showed that 6-OHDA induced a reduction of brain noradrenaline level in stress-resistant rats and a reduction of dopamine level in nonresistant animal. It is suggested that more demonstrative behavioural disturbances induced by 6-OHDA in stress-resistant rats are connected with deficit of brain noradrenaline.     

Neuromediator mechanisms of the effect of the antihistamine agent dimebone on the brain

Dimebone was shown to inhibit monoamine oxidase (MAO) deaminating dopamine and serotonin, decrease dopamine metabolism in the basal ganglia of the rat brain, increase noradrenaline level and depress dopamine deamination in the hypothalamus. Dimebone first increased and then diminished the release of dopamine in the cortex, with the concomitant MAO activation and the increase in dopamine and noradrenaline levels. The in vitro experiments have demonstrated that dimebone (10(-4)) preferentially inhibited MAO activity, type B and dopamine deamination in homogenates of different rat brain structures. The role of MAO inhibition in the mechanism of dimebone action on the catecholamine metabolism in the brain structures and its stimulating effect on CNS are discussed.     

Action of dopamine on the human iris

Dopamine eye drops produce marked dilatation of the pupil in man. This mydriatic effect is inhibited by pretreatment with guanethidine. It is therefore concluded that dopamine acts indirectly via adrenergic nerve endings, rather than exerting a direct effect on adrenergic receptors in the dilator pupillae muscle. In this respect dopamine resembles the phenyl-alkylamines, such as tyramine, rather than the catecholamines, adrenaline and noradrenaline.If dopamine acts by releasing noradrenaline from adrenergic nerve endings, high concentrations of dopamine could lead to depletion of noradrenaline stores, since synthesis might be unable to keep pace with release. This could be the explantion for the orthostatic hypotension found in patients taking L-dopa for Parkinsonism.     

Changes in the catecholamine content of brain structures in rats subjected to immobilization stress

The changes in DOPA and catecholamine (adrenaline, noradrenaline, dopamine) levels were investigated in noradrenaline- and dopamine-synthesizing brain nuclei of Wistar rats after prolonged immobilization stress on catecholamine analyzer (BAS, USA) using HPLC technique. Distinct DOPA and catecholamine changes were observed in locus ceruleus + nucleus subceruleus (1. c + n. sc) and substantia nigra at any stage after immobilization (right after immobilization and 15 and 30 days later). The most prominent alterations in noradrenaline content were detected in 1. c + n. sc. 30 days after immobilization NA level in these nuclei was 1.5 times higher, as compared to the control one. It is suggested that the increasing noradrenaline level in 1. c + n. sc. plays a defensive role in survival of rats after immobilization stress.     

Participation of pentagastrin and oxytocin in organizing neural activity of the dorsal hippocampus during result- and conflict-oriented feeding behavior in rabbits

Single unit activity of CA3 dorsal hippocamp has been registered in free moving rabbits. The influence of microiontophoretic application of pentagastrin and oxytocin on neuronal involvement into feeding or defensive behaviour has been studied. The change of the dominant feeding motivation to defensive was shown to cause resettings in the typical feeding activity of most neurons. Microiontophoretic application of pentagastrin induces typical feeding activity even if rabbits demonstrate defensive behaviour. It is believed that pentagastrin presence in perineuronal area leads to the involvement of most hippocampal neurons into the organization of the feeding behaviour.     

Effect of morphine on the concentration of monoamines in the emotiogenic zones of the hypothalamus in adult and old rats

The content of monoamines in the emotiogenic hypothalamic zones has been shown to noticeably change with aging of rats. The level of noradrenaline and serotonin increased in the ventromedial nucleus of the hypothalamus, while the concentration of noradrenaline increased in the lateral hypothalamic zone. Single i.p. injections of 10 mg/kg morphine evoked qualitatively different shifts in the monoamine concentrations in the hypothalamic emotiogenic zones of the rats of different ages: the level of dopamine increased in adult animals, while the levels of noradrenaline and serotonin dropped in old rats. It is supposed that in old age the effect of morphine on dopaminergic structures in the emotiogenic hypothalamic zones becomes more moderate, whereas that on the noradrenergic and serotonergic structures is facilitated. The age-related specificities of the morphine effect on the monoaminergic regulation of the emotiogenic hypothalamic zones can determine considerable modifications of a psychotropic effect of the drug in old age.     

Mechanisms of stomach secretion in dogs infused with histamine, carbacholine and pentagastrin

In chronic experiments on dogs with Basov 's stomach fistulas and pvc catheters implanted into the jugular vein the authors studied the effects of noradrenaline and adrenaline (30 mg/kg) on gastric secretion stimulated by pentagastrin. It was shown that the adrenagonists suppressed the pentagastrin-stimulated gastric secretion. The suppressing effect lasted 90 minutes after discontinuation of adrenaline or noradrenaline infusion.     

Deep brain stimulation of the accumbens increases dopamine,serotonin, and noradrenaline in the prefrontal cortex

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is effective in treatment‐refractory obsessive‐compulsive disorder and major depressive disorder. However, little is known about the neurobiological mechanisms underlying the rapid and effective changes of DBS. One of the hypotheses is that DBS modulates activity of monoamine neurotransmitters. In this study, we evaluated the effects of DBS in the NAc core on the extracellular concentration of monoaminergic neurotransmitters in the medial (mPFC) and orbital prefrontal cortex (OFC). Freely moving rats were bilaterally stimulated in the NAc core for 2 h while dopamine, serotonin, and noradrenaline were measured using in vivo microdialysis in the mPFC and the OFC. We report rapid increases in the release of dopamine and serotonin to a maximum of 177% and 127% in the mPFC and an increase up to 171% and 166% for dopamine and noradrenaline in the OFC after onset of stimulation in the NAc core. These results provide further evidence for the distal effects of DBS and corroborate previous clinical and pre‐clinical findings of altered neuronal activity in prefrontal areas.