Showing papers in "Journal of Neural Transmission in 1972"

An experimental model of tardive dyskinesia

Abstract: There are numerous clinical and experimental similarities between amine induced stereotyped behavior and tardive dyskinesia. The results presented here show that chronic pretreatment of guinea pigs with chlorpromazine produces a persistent reduction in the amounts of amphetamine or apomorphine needed to induce stereotyped behavior. It is suggested that chlorpromazine pretreatment may alter the sensitivity of the striatal dopaminergic receptors to dopamine. The alteration in receptor site responsiveness produced by prolonged chlorpromazine pretreatment may be analogous to the neuroleptic induced tardive dyskinesias. The same dopaminergic mechanism may underlie both the amine stereotyped behavior seen in animals and tardive dyskinesias in man, while lingual-facial-buccal dyskinesias may be the human equivalent of the stereotypies seen in animals when the dopaminergic response in the striatum is increased.

The effect of L-tryptophan and some psychotropic drugs on the formation of 5-hydroxytryptophan in the mouse brain in vivo

Abstract: L-Tryptophan and various agents known to interfere with the brain monoamines were injected intraperitoneally to mice. Subsequently, the accumulation of 5-hydroxytryptophan (5-HTP) in the brain induced by the intraperitoneal injection of the decarboxylase inhibitor Ro 4-4602 was investigated. Also the tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the brain were measured.

Potentiation of phenothiazines by -methyltyrosine in treatment of chronic schizophrenia.

Abstract: Five patients, suffering from chronic schizophrenia with stationary symptomatology were treated with a combination of a phenothiazine and the tyrosine hydroxylase inhibitorα-methyltyrosine. The antipsychotic action of the neuroleptic agent was markedly potentiated, permitting a considerable reduction of the neuroleptic dosage required for controlling the condition. The observations support experimental data indicating that neuroleptics act by interfering with central synaptic catecholamine transmission. The possible usefulness of an inhibitor of catecholamine synthesis in combination with a neuroleptic for controlling mental disorders is discussed.

Importance of central catecholamines in the mediation of lordosis behaviour in ovariectomized rats treated with estrogen and inhibitors of monoamine synthesis.

Abstract: The effect ofα-methyl-p-tyrosine methylester hydrochloride (α-MT) (100 mg/kg i.p.) orp-chlorophenylalanine methylester hydrochloride (PCPA) (150 mg/kg i.p.) on lordosis behaviour in estrogen pretreated spayed rats was investigated. The effect ofα-MT was studied 1, 2, 4, 8 and 26 hours after the drug injection and the observations after PCPA were done 2, 4, 8, 26 and 50 hours after the injection. Facilitation of lordosis was seen 2–8 hours after both treatments. Biochemical experiments were done in parallel and the injection of eitherα-MT or PCPA resulted in a transient decrease in brain catecholamines which was correlated in time with the facilitation of the lordosis response. Furthermore PCPA resulted in a gradual decline in brain 5-HT. However, when 5-HT depletion was most pronounced and the brain catecholamines had returned to control levels no increase in lordosis behaviour occurred. Our findings suggest a role for central catecholamines in the mediation of lordosis behaviour in ovariectomized estrogen-drug-treated rats.

Observations on the dopaminergic nature of hyperthyroid chorea.

Abstract: Hyperthyroid chorea is felt to be related to an increased response of striatal dopamine receptors to dopamine. This suggestion is supported by the observation that an agent which blocks dopamine receptors improved chorea in a hyperthyroid patient. An inverse relationship between thyroid status and brain dopamine turnover as estimated by CSF HVA levels was demonstrated. This observation suggests that hyperthyroidism increases the sensitivity of dopamine receptors to dopamine. This is the first example of increased receptor site sensitivity in the brain unassociated with a known structural lesion. An analogous mechanism is felt to be related to Huntington's chorea, but in this disease the increased receptor site response is due to structural alterations of the diseased neuron.

The balance of biogenic amines as condition for normal behaviour

Abstract: An accumulation of norepinephrin, serotonin and dopamin exists in the brainstem. A decrease of biogenic amines in the brains of Parkinson's cases has been demonstrated. A substitution by the precursor L-DOPA produces an increase of dopamin in the brain and a decrease of serotonin. The high level of dopamin improves the akinesia and the depletion of serotonin causes a toxic delir. A substitution by l-tryptophan restores the balance and the Dopa-psychosis disappears.

Effects of tetrabenazine on lordosis behaviour and on brain monoamines in the female rat.

Abstract: The time course of action of tetrabenazine (TBZ), 2 and 10 mg/kg i.p., on lordosis behaviour and on brain monoamines in ovariectomized estrogen pretreated female rats, was studied. The administration of TBZ (2 mg/kg) produced a decrease in brain DA and an increase in the number of lordosis, whereas 10 mg/kg of TBZ resulted in the same increase in lordosis behaviour as 2 mg/kg and a significant decrease in NA, DA and 5-HT. The results suggest that a decrease in brain monoamine levels, especially DA, facilitates lordosis behaviour in estrogen-TBZ treated female rats.

Amantadine actions on acetylcholine and GABA in striatum and substantia nigra of rat in relation to behavioral changes.

Abstract: A relatively high dose of amantadine (100 mg/kg i.p.) causes rigidity with humpback and tremor-like movements, but at a milder degree than harmaline. The amantadine induced syndrome is later accompanied with locomotor hyperactivity. Biochemically amantadine produces an increase of acetylcholine (ACh) content (100%) in the striatum, but with no effect on the striatal serotonin or dopamine, while GABA is increased 17% in striatum and 23% in substantia nigra. The enzyme activities involved in synthesis and degradation of ACh and GABA, namely glutamic acid decarboxylase, GABA-transaminase, and cholineacetyltransferase, are not altered after amantadine hydrochloride. The acetylcholinesterase activity in the striatum appears to show a slight decrease. The rigidity and the tremor-like movements after amantadine can be explained by the increased striatal acetylcholine as in the case of harmaline. The locomotor hyperactivity and the circling movements after amantadine hydrochloride may result from the inhibition of recurrent nigro striatal (dopaminergic) fibers influenced by the increased GABA activity in the substantia nigra, thereby causing disinhibition of the pallidar structures for locomotor activity. The cause of stereotypy and convulsions requires further investigations.

Hypophagia, hypodipsia, and hypoactivity following electrolytic lesions in the dorsomedial hypothalamic nuclei of mature rats of both sexes.

Abstract: Electrolytic bilateral lesions of the dorsomedial hypothalamic nucleus of both female and male mature rats resulted in hypophagia, hypodipsia and decreased spontaneous running activity. The latter is not associated with increased fat deposition. Resting oxygen consumption was reduced in both sexes, but significantly only in the males. Thyroid weight was normal in both sexes but ovaries and adrenals were lighter in the females and the pituitary was lighter in the male rats with lesions. The data show that the dorsomedial hypothalamic nucleus is involved in hypothalamic mechanisms controlling food intake, water intake and spontaneous activity not only in the weanling rat as previously demonstrated, but in the mature rat as well.

The effects of 6-hydroxydopamine pretreatment on the accumulation of dopa and dopamine in brain and peripheral organs following L-dopa administration.

Abstract: The capacity of brain and peripheral organs to accumulate dopamine following intraperitoneal l-dopa was not impaired in rats whose catecholamine-containing nerve terminals had been destroyed by pretreatment with intracisternal or intraperitoneal 6-hydroxydopamine. These findings indicate that the uptake of exogenous l-dopa and its conversion to dopamine are not restricted to cells that normally synthesize and contain catecholamines.

Diurnal changes in sympathetic nerve endings in the mouse pineal: Semiquantitative electron microscopic observations

Abstract: Sympathetic nerve endings of the mouse pineal were examined by qualitative and semiquantitative electron microscopy at various times of the day under usual lighting conditions (12 hours of light and 12 hours of darkness per day). The nerve endings contained a mixed population of both small granular vesicles and small agranular vesicles. The small granular vesicles, 650 A in mean diameter, were characteristic of adrenergic nerves. They were subdivided, on the basis of the size of the granules, into two types, Types 1 and 2. The Type 1 granular vesicles contained a dense granule which, though varying in size, did not completely fill the vesicle and was often located eccentrically within the vesicle. The Type 2 granular vesicles had a large granule that almost filled the vesicle. The small agranular vesicles were also subdivided, according to their shape, into two types, Types 1 and 2. The Type 1 agranular vesicles were spherical with a mean diameter of 650 A, and the Type 2 agranular vesicles, elliptical or flat, measuring 800×300 A in mean long and short diameters. The proportions of vesicles of the above types, except for the Type 1 agranular vesicles, varied diurnally in correlation with the cycles of day and night. During the light period of the day, both the granular and agranular vesicles were almost constant in proportion. After the onset of darkness, however, all the vesicles except for Type 1 agranular vesicles underwent remarkable changes in the proportion of population. The proportion of Type 1 granular vesicles decreased remarkably until midnight, but at the end of the dark period it was increased again. Simultaneously with a decrease in proportion, the granules appeared to decrease in size. After the onset of the light period the Type 1 granular vesicles increased in proportion. The Type 2 granular vesicles, though less numerous in number, also showed the same tendency in proportion as the Type 1 granular vesicles, and they were almost absent at midnight. The small agranular spherical vesicles of Type 1 remained almost unchanged in proportion throughout the light and dark periods. The Type 2 agranular flat vesicles increased after the onset of darkness. At the end of the dark period they were again reduced in proportion. In addition to the four types of small vesicles, occasional large granular vesicles having a diameter of more than 1000 A were also contained within the nerve endings. They remained unchanged in both proportion and nature throughout the day.

Age-dependent effects of 5-methoxytryptophol and melatonin on testes and comb growth of the white leghorn (Gallus domesticus L.)

Abstract: Testes weights of white leghorns of the same age or of equal body weight vary considerably. Experiments on the effects of pinealectomy, administration of pineal extracts or indolic compounds on the testes weights therefore require better parameters. Cockerels having a similar initial comb size prove to have testes of similar weights. Experiments using this parameter permit a more exact comparison of control and experimental animals. Administration of 5-methoxytryptophol and melatonin in increasing concentrations to juvenile, maturing and adult white leghorn males shows an age-dependent activity. In juvenile birds, the testes and comb growth are stimulated by 5-methoxytryptophol and melatonin, whereas in maturing and adult cocks both indolic compounds show an inhibitory effect. It appears that the effect of 5-methoxytryptophol is more specific than that of melatonin in juvenile as well as in maturing and adult white leghorns.

Alterations in the distribution of yellow fluorescing rabbit pinealocytes produced by P-chlorophenylalanine and different conditions of illumination.

Abstract: Fluorescence Microscopy Changes in the density of yellow autofluorescent and serotonincontaining pinealocytes in the rabbit pineal gland have been studied under different experimental conditions such as p-chlorophenylalanine, environmental lighting and permanent darkness, using fluorescence microscopy. The yellow autofluorescent pinealocytes (Type II), particularly present in a circumscript area of the organ, increased in number during treatment of the animals with pCPA as well as during the night under environmental lighting conditions. This increase probably accurred at the cost of the decrease in number of serotonin-containing pinealocytes (Type I) in the same area, originally present. Moreover it could be demonstrated that under environmental lighting conditions both, the number of Type I and Type II cells, showed a day and night rhythm. During continuous darkness the circadian rhythm in the serotonin content of the Type I cells persists. Evidently, this rhythm is not controlled by exogenous environmental lighting conditions but endogenously. In contrast to the persisting circadian serotonin rhythm, no such fluctuations could be observed in the yellow autofluorescing compound in the Type II cells.

Effects of p-chlorophenylalanine and a monoamine oxidase inhibitor on the 5-hydroxytryptamine in the spinal cord and transection.

Abstract: Treatment with the monoamine oxidase inhibitor nialamide (500 mg/kg i.p., 2.5 and 5 h) produced in the caudal and cranial half of the spinal cord an increase in 5-hydroxytryptamine which was of the same magnitude in intact rats and in rats acutely spinalized midthoracically. Similar results were obtained after reserpine pretreatment. The nialamide-induced increase in 5-hydroxytryptamine caudal to a transection was slightly reduced after 2 days and completely inhibited after 3 weeks.

Vago-sympathetic modulation of gastric mechanoreceptors: Effect of distention and nutritional state

Abstract: Unit discharge evoked in gastric afferents by tactile stimulation of the frog's stomach was inhibited by electrical stimulation of gastric vagi and facilitated by cervical sympathetic stimulation. The inhibition or the facilitation of the evoked response depended on the mode and parameters of stimulation used. The tactually-evoked activity was also inhibited by gastric distention in well-fed animals (Type-I). This inhibition was released by gastric vagotomy, while cervical sympathectomy had no appreciable effect on the evoked inhibitory response.

Role of the cerebellum in the control of gastro-intestinal motility.

Abstract: 172 points In the cerebellar vermis and the fastigial nucleus were stimulated to observe the effects on gastric and duodenal motility of the cat. Stimulation of the nodule consistently increased gastric motility producing tonic as well as rhythmic contractions. In general, whenever the stimulation of a cerebellar point increased the gastric motility, duodenal motility was simultaneously inhibited. In these cases, however, the duodenum was markedly activated during the post-stimulation period. Stimulation of the uvula elicited responses which were dependent on the initial state of gastric activity. At high basal pressures, gastric motility was inhibited by cerebellar stimulation while, at low basal pressures, it was increased. Stimulation of points in the lobulus centralis, the lingula, and the fastigial nucleus produced different types of responses varying from no effect to various grades of inhibitory or excitatory changes. Changes in gastric and duodenal motility bore no specific relation to the simultaneously recorded changes in systemic arterial pressure. Responses exhibiting increase as well as those exhibiting decrease of gastric motility were observed to be associated with a rise in blood pressure. In most animals these responses were also accompanied by respiratory excitation.

Biochemie der Depression

Abstract: Trotz bedeutender Fortschritte auf dem Gebiet der biochemischen Depressionsforschung, die zur Klarung einer Reihe wichtiger, vor allem methodischer Fragen fuhrten, sind wir noch weit von einer biochemischen Losung der Depression entfernt. Die Interpretation der teilweise widerspruchlichen Urin- und Liquorergebnisse bereitet heute noch grose Schwierigkeiten. An die Aufklarung der Ursache der einen oder anderen hypothetischen Stoffwechselstorung bei der Depression ist man heute experimentell noch nicht herangegangen. Viele Prozesse selbst des normalen Nervensystems sind uns noch weitgehend unklar und unbekannt, vor allem auch die Steuerung zyklischer Ablaufe, die fur die Depression von besonderer Bedeutung sind. Es wird noch umfangreicher, aber lohnender Anstrengungen bedurfen, die so einfach und einleuchtend klingenden 5-HT- und NA-Hypothesen der Depression zu beweisen oder sie zu widerlegen.

[Effect of hydrocortisone on the amount of Gomori-positive substances in the zona externa infundibuli of bilaterally adrenalectomized rats].

Abstract: Bilaterale Adrenalektomie fuhrt bei der Ratte zu einer Vermehrung „Gomori-positiver“ Granula in der Zona externa infundibuli. Die Menge der Granula ist durch Gabe von Hydrocortison zu beeinflussen.

On the site of action of reserpine on ACTH secretion

Abstract: The studies were concerned with the site in the CNS of the action of reserpine on pituitary ACTH secretion. The medial basal hypothalamus (MBH) was totally or partially deafferented (interrupting the anterior, the posterior and superior or the posterior connections of the region and leaving intact all the other pathways), the fornix was transected or a lesion was placed in the medial ventral tegmentum of the mesencephalon, and following all these interventions plasma corticosterone levels were determined before reserpine treatment and four hours after drug administration (giving 3.0–3.5 mg/kg b.w. i.p.). In the intact rats reserpine caused a 3–5 fold increase in plasma corticosterone concentration. No elevation in blood corticoid levels occurred if the drug was administered to rats in which the MBH was completely deafferented. Similar results were obtained when only the anterior connections of the MBH were interrupted. In contrast, severance of the afferents coming to the MBH from both sides and from above, or from posterior, transection of the fornix, or a lesion in the medial ventral tegmentum of the mesencephalon did not block the mentioned effect of reserpine. The drug given to intact rats for nine days (0.7 mg/kg b.w. daily i.p.) induced a well-known marked increase in adrenal weight. Complete deafferentation of the MBH also interfered with this effect. — The data suggest that (1) the reserpine-induced CRF release is not directly exerted on the MBH; (2) the critical afferents essential for the pituitary ACTH response to reserpine reach the MBH from an anterior direction; (3) hippocampal and mesencephalic structures having direct contact with the MBH are not primarily responsible for the reserpine effect on ACTH.

Light and electron microscopic studies of normal and heterogeneously regenerated ganglionic synapses of the dog.

Abstract: Heterogeneous synapses in the superior cervical ganglion of the dog were obtained by regeneration of phrenic nerve fibres, after cutting and degeneration of the normal preganglionic fibres. The shape of the terminal of the regenerated fibres and the ultrastructural features of the newly formed synapses are very similar to those present in the normal ganglion. Thus, the fundamental role of the postsynaptic element in the determination of the cytological characteristics of these synapses is evident. A subsynaptic apparatus, in the shape of a layer of dense patches, was observed in a certain number of normal and of regenerated synapses. A special type of small vesicles, 150 A in diameter, was found to be present in the vicinity of the dense projections of many active zones; their functional role is, so far, not established.