The hyperkinetic syndrome following long-term haloperidol treatment: Involvement of dopamine and noradrenaline

Summary Mice withdrawn for 7 days from a 35-day treatment period with haloperidol (3 mg/kg/day) displayed significantly greater spontaneous locomotor activity (hyperkinesia) than animals withdrawn from the vehicle. The hyperkinesia was antagonized by phenoxybenzamine (an-adrenergic receptor antagonist) and by FLA-63 (a dopamine--hydroxylase inhibitor) but not by haloperidol (a dopamine receptor antagonist).-Methyl tyrosine (a tyrosine hydroxylase inhibitor) was effective in antagonizing the hyperkinesia and this blockade by-methyl tyrosine could be completely reversed by the administration of a low dose of the catecholamine precursor, DOPA. The data suggest that noradrenergic systems are of importance for the manifestation of the hyperkinetic syndrome seen in mice withdrawn from long-term haloperidol treatment.     

Chronic treatment with the potential antidepressant drug rolipram: the effect on the behavioural responses to adrenergic and dopaminergic receptor agonists with some biochemical correlates

Summary We studied the effect of acute and chronic treatment with rolipram, a potential antidepressant drug, on the behavioural responses induced by adrenergic and dopaminergic receptor agonists in mice and rats, and on (³H)prazosin and (³H)dihydroalprenolol binding to cortical membranes and whole brain noradrenaline and dopamine utilization in rats. Chronic, but not acute, administration of rolipram potentiated a behavioural response mediated through central ₁-adrenoceptors, attenuated an ₂-adrenoceptormediated response and inhibited a-adrenoceptor-mediated response. Neither treatment affected the behavioural responses to dopaminergic stimulants. Repeated treatment with rolipram decreased the density of cortical (³H)dihydroalprenolol, but not (³H)prazosin bindings sites, and reduced brain noradrenaline, but not dopamine utilization. These results suggest that chronic administration of rolipram induces the down-regulation of the central- and ₂-adrenoceptors and enhances the responsiveness of the central ₁-adrenoceptors with no apparent changes in the ₁-adrenoceptor density.     

Chronic cobalt-induced epilepsy: Noradrenaline ionophoresis and adrenoceptor binding studies in the rat cerebral cortex

Summary Several studies indicate that brain noradrenaline (NA) depletion facilitates the occurrence of epileptogenic syndromes in various animal models. In cobalt-induced epilepsy in the rat, seizure activity is associated with a cortical NA denervation. In order to search for cortical adrenoceptor modifications, inonophoretic studies and adrenoceptor binding assays were performed. At the period of maximal seizure activity, there was a significant supersensitivity of cortical neurons to the ionophoretic application of NA. An increase in the density of-adrenoceptor binding sites was observed. No modification in ₁- and ₂-adrenoceptor binding sites was found. This suggests that in cobalt-induced epilepsy there is a denervation supersensitivity which rests on a selective involvement of-adrenoceptors.     

Kritische Anmerkungen über die Gedankeneingebung

Zusammenfassung Gedankeneingebung ist eines der Symptome ersten Ranges im Sinne von Kurt Schneider. Schon früher hatte Karl Jaspers eine feinere Trennung vollzogen: Er unterschied zwischen der Gedankeneingebung in einem engeren Sinne und gemachten Gedanken. Indessen haben die meisten deutschen und englischen Autoren die Jasperschen Kriterien dieser Unterscheidung verschmolzen und dadurch den Gebrauch des Terminus ausgeweitet. Auch Kurt Schneider und Weitbrecht sprachen von Gedankeneingebung, gemachten Gedanken und Gedankenbeeinflussung, als ob diese Phänomene identisch seien. Demgegenüber bietet die Jaspersche Differenzierung eine Trennschärfe bei der Erfassung psychopathologischer Symptome, auf die nicht verzichtet werden sollte. Logischerweise und aus praktischen Gründen läßt sich diese Differenzierung auf alle gemachten oder Beeinflussungserlebnisse ausdehnen, so daß man vier Aspekte solcher Phänomene unterscheiden kann. Einige differential-diagnostische Überlegungen hinsichtlich der Gedankeneingebung werden abschließend kurz besprochen.Professor H. -H. Meyer zum 65. Geburtstag herzlich zugeeignet.     

Cytoplasmic and axoplasmic density variations in relation to hyperactivity

Summary The density of the cytoplasm and axoplasm of the anterior horn cell in rats was determined by X-ray microradiography. The average density of the cytoplasm of more than 400 cells from control rats was 0.31 g/³, while that of over 600 cells from rats fed IDPN (- iminodipropionitrile) was 0.43 g/³.Hyperactivity developed during the first 5 weeks and was associated with a gradual increase in cytoplasmic density to 0.51 g/³.At 6 weeks there was a drop in density to 0.36 g/³ which coincided with the appearance of axonal balloons having a density of 0.17 g/³.During the 7–12th week on the diet, the cytoplasmic density showed a gradual increase to 0.59 g/³ and the balloons to 0.29 g/³.The volume of the nerve cells remained fairly constant. The density increases were discussed in relation to hypertrophy, dystrophy, and hyperactivity.

---

Zusammenfassung Die Dichte des Cytoplasmas und Axoplasmas der Vorderhornzellen von Ratten wurde durch Röntgenmikroradiographie bestimmt. Die mittlere Dichte des Cytoplasmas von mehr als 400 Zellen der Kontrollratten war 0,31 g/³, während die mittlere Dichte von mehr als 600 Zellen der Ratten, die mit IDPN (- iminodipropionitrile) gefüttert waren, 0,43 g/³ war.Hyperaktivität entwickelte sich während der ersten 5 Wochen und war mit einer progressiven Zunahme der Cytoplasmadichte bis auf 0,51 g/³ verbunden.Nach 6 Wochen sank die Dichte auf 0,36 g/³. Diese Tatsache traf mit dem Auftreten der Axonauftreibungen zusammen, die eine Dichte von 0,17 g/³ hatten.Nach 7–12 Wochen zeigte die Cytoplasmadichte eine progressive Zunahme auf 0,59 g/³ und die der Auftreibungen eine Zunahme auf 0,29 g/³.Das Volumen der Nervenzellen blieb ziemlich konstant.Die möglichen Zusammenhänge zwischen Zunahme der Dichte, Hypertrophie, Dystrophie und Hyperaktivität werden dargestellt.

---

---

Supported by U. S. Public Health Grant NB 1305.     

A 3’-UTR polymorphism in the oxidized LDL receptor 1 gene increases Aβ40 load as cerebral amyloid angiopathy in Alzheimer’s disease

It is presently unclear whether polymorphic variations in the oxidized low-density lipoprotein receptor 1 (OLR1), or low-density lipoprotein receptor-related protein 1 (LRP1), genes act as risk factors for Alzheimers disease (AD). In the present study, we have investigated the extent of amyloid protein (A) deposition as cerebral amyloid angiopathy (CAA) or senile plaques (SP) in relationship to OLR1 +1071 and +1073 polymorphisms and LRP1 C766T polymorphism in patients with AD There was an increased A₄₀ load as CAA, but not as SP, in frontal cortex of AD patients carrying OLR1+1073 CC genotype, compared to those with CT, TT or CT+TT genotypes, but only in those individuals without apolipoprotein (APOE) 4 allele. No differences in total A or A₄₂ load as CAA or SP between OLR1+1073 genotypes was seen, nor were there any differences between OLR1+1071 and LRP1 genotypes for any measure of A. Present data suggests that homozygosity for the C allele for OLR1+1073 polymorphism, selectively in individuals without APOE 4 allele, may impair clearance of A, and particularly A₄₀, from the brain across the blood-brain barrier, leading to its diversion into perivascular drainage channels, thereby increasing the severity of CAA in such persons.     

A simplified radioimmunological method for the determination of human β-endorphin in cerebrospinal fluid

Summary Human -endorphin-like immunoreactive substances ( _h -EI) in human cerebrospinal fluid (CSF) were determined radioimmunologically. The cross reactivity of the antibodies to human -endorphin ( _h -E) amounted to 40% for human -lipotropin ( _h -LPH) whilst it was less than 1% for leu-and metenkephalin, - and -endorphin, fraction I and II [5], substance P and -MSH. Prior to radioimmunological determination, an adsorbtion of _h -EI from CSF with silicic acid was carried out and followed by a desorbtion, using a mixture of aceton/hydrochloric acid. This method was chosen because the ratio of _h -LPH to _h -E in the desorbat can be shifted in favour of _h -E owing to the variation in recoveries r ( =33%, =64%). On the one hand, this enables a more specific determination of _h -E and, on the other hand, and separation of any peptidase than may be present [9]. An adsorbtion/desorbtion of 2 ml CSF suffices to prove the presence of 20–150 pg/ml (6–48 fmol/ml) of _h -EI.The CSF of 28 patients with various neurological diseases was examined and 24 of them had concentrations of 20–70 pg/ml _h -EI. The remaining four, which had concentrations less than 20 pg/ml, came from meningitis patients undergoing corticoid therapy.A purchasable RIA kit was tested for its determination of _h -E and was found to be unsuitable.

---

Zusammenfassung Beta-human-Endorphin-like immunreaktive Substanzen ( _h -EI) im menschlichen Liquor (CSF) wurden radioimmunologisch bestimmt. Die Kreuzreaktivität des von uns eingesetzten Antikörpers gegen Beta-human-Endorphin ( _h -E) zum Beta-human-Lipoprotein ( _h -LPH) betrug 40%, während sie zu Leu- und Met-Enkephalin, Alpha- und Gamma-Endorphin, Fraktion I und II nach Terenius [10], Substanz P und Alpha-MSH geringer war als 1%. Vor der radioimmunologischen Bestimmung wurde eine Adsorption von _h -EI aus CSF an Kieselsäure mit anschließender Desorption mittels eines Gemisches aus Aceton/Salzsäure durchgeführt. Diese Methode wurde gewählt, weil sich dadurch das Verhältnis von _h -LPH zu _h -E im Desorbat zugunsten von _h -E aufgrund der unterschiedlichen Recoveries R ( =33%, =66%) verschob. Damit wird einerseits eine erhöhte Spezifität bei der Bestimmung von _h -EI und andererseits eine Abtrennung von eventuell vorhandenen Peptidasen erreicht. Eine Adsorption/Desorption aus 2 ml CSF genügt, um _h -EI von 20–150 pg/ml (6–48 fmol/ml) nachzuweisen.Patienten (n=28) mit verschiedenen neurologischen Erkrankungen wiesen Werte von 20–70 pg/ml auf. Vier Liquores unter 20 pg/ml stammten von Meningitis-Patienten, welche unter einer Corticoidtherapie standen.Ein käuflicher RIA-Kit wurde auf seine Eignung zur Bestimmung von _h -E untersucht und verworfen.

     

Positron emission tomographic studies on aromatic L-amino acid decarboxylase activity in vivo for L-dopa and 5-hydroxy-L-tryptophan in the monkey brain

Summary The regional brain kinetics following 5-hydroxy-L-(-11 C)tryptophan and L-(-11 C)DOPA intravenous injection was measured in twelve Rhesus monkeys using positron emission tomography (PET). The radiolabelled compounds were also injected together with various doses of unlabelled 5-hydroxy-L-tryptophan or L-DOPA. The radioactivity accumulated in the striatal region and the rate of increased utilization with time was calculated using a graphical method with back of the brain as a reference region. The rate constants for decarboxylation were 0.0070 ± 0.0007 (S. D) and 0.0121±0.0010min^–1 for 5-hydroxy-L-(-11C)tryptophan and L-(-11 C)DOPA, respectively. After concomitant injection with unlabelled 5-hydroxy-L-tryptophan, the rate constant of 5-hydroxy-L-(-11 C)tryptophan decreased dose-dependently and a 50 percent reduction was seen with a dose of about 4mg/kg of unlabelled compound. A decreased utilization rate of L-(-11 C)DOPA was seen only after simultaneous injection of 30 mg/kg of either L-DOPA or 5-hydroxy-L-tryptophan. This capacity limitation was most likely interpreted as different affinity of the striatal aromatic amino acid decarboxylase for L-DOPA and 5-hydroxy-L-tryptophan, respectively.     

Monoamine metabolism in rat brain regions following long term alcohol treatment

Summary Female Wistar rats (150–200 g) were treated with ethanol (15% w/v) for 21 days and compared with control rats given water. Ethanol administration produced a reduction of fluid and food consumption and changes in the metabolism of cerebral monoamines. There was an increase in serotonin (5-HT) turnover statistically significant in the striatum, and a decrease in noradrenaline (NA) turnover in ethanol rats as compared to controls.Endogenous NA levels were significantly increased in the diencephalon and dopamine (DA) levels were increased in the striatum. After inhibition of catecholamine synthesis with-methyltyrosine (-MT), NA depletion was significantly retarded but no changes in DA depletion were noted. DOPA accumulation after decarboxylation inhibition showed no significant change in any brain region studied.     

Types of authority and two problems of psychiatric wards

This paper concerns the relationship between authority structures and two problems reported in the literature as common to milieu or therapeutic community wards. Psychiatric wards with rational-legal and charismatic authority structures are found more likely to experience mood and morale swings on the part of patients and staff and to spend excessive time and energy changing ward rules.     

Peripheral chromatolysis after transection of mouse facial nerve

Summary Adult male mice, after transection of the facial nerve near the stylomastoid foramen, were sacrificed at predetermined intervals by the two-step perfusion fixation with a modified Heidenhain's Susa solution and subsequently autopsied after a delay of at least four hours.The normal population of neurons consists of one small form with small basophil granules and one large with numerous coarse granules.The initial change demonstrable in the large neuron 12 hours post-operatively is the loosening of cytoplasmic basophil material which proceeds to a disappearance peripherally at the 24-hour stage; simultaneously an increased staining of the non-particulate cytoplasm takes place. The disintegration of basophil material reaches a maximum 9 days post-operatively and from 12 through 49 days post-operatively occurs an increasingly prominent restoration of basophil material near the nuclear membrane. At the 49-day stage the number of recovered large neurons is small and many are lost. At the 9-and 12-days post-operative stages appears a dark abnormal neuron of questionable origin. Histiocyte reaction is apparent by an increasing number of mitotic figures along vascular walls from the 2nd day to the 9th day; the invasion of microglia cells occurs from the 3rd day and clusters of microglia from the 9th day.The sequential changes in the small neuron are somewhat similar to those in the large type. In its recovered forms, it exceeds the large in number, but is abnormal in color and poorly supplied with basophil material.A concurrent study of the rabbit facial nucleus discloses two types of neurons which after axotomy react differently but mimic at a slower rate the sequence in mice.The cardinal feature of acute retrograde cell changes is the inability of the cytoplasm to store properly its basophil material, as first manifested by a loosening of texture with an early disappearance along the cell periphery and then by haphazard deposition of granular material.With 2 Figures in the Text     

Lack of effect of a behaviorally active dose ofα-melanotropin on biochemical indices of dopaminergic neuronal activity in the rat

Summary An attempt was made to correlate behavioral changes in the male rat following an intracerebroventricular (ICV) injection of-melanotropin (-MSH, 10g) with biochemical estimates of the activities of nigrostriatal, mesolimbic, tuberoinfundibular and tuberohypophyseal dopaminergic neurons. ICV injection of-MSH elicited body snaking, stretching, yawning and penile erections. The concentrations of dopamine (DA) and dihydroxyphenylacetic acid and the rate of DA synthesis (accumulation of DOPA after the inhibition of DOPA decarboxylase) in the striatum, nucleus accumbens, olfactory tubercle, septum, median eminence and posterior pituitary were unaltered at any time (30–180 min) after ICV injection of-MSH. Intraperitoneal injection of-MSH (100g/kg) also failed to change the rate of DOPA accumulation in these brain regions. These results imply that the behaviors observed after-MSH are not associated with changes in the activity of DA neurons.Visiting professor from Fukuoka University, Fukuoka, Japan.     

Meningiomas with a non-meningotheliomatous component

Summary Seven cases of meningiomas with pseudopsammoma bodies have previously been described in the literature. Two additional cases are presented. Electron microscopy of the cells surrounding the pseudopsammoma bodies reveals an ultrastructure different from that of the meningotheliomatous cells. It is concluded that meningotheliomatous meningiomas with pseudopsammoma bodies are mixed tumours, including a non-meningotheliomatous component, the origin and significance of which is uncertain.     

“Dorm D:” A form of group psychotherapy with children in residential treatment

In this paper, Dorm D, a form of group psychotherapy for severely emotionally disturbed children, is described, along with the inpatient setting in which this specific form of treatment evolved. Three paradigms of Dorm D are presented as prototypes for conceptualizing groups in the inpatient residential setting, followed by a discussion of the technical demands evoked by all three paradigms, including limit setting. The paper is intended as an illustration of how classical group therapy techniques can be expanded and modified to provide a viable treatment alternative in a great variety of settings in which children are placed into groups.     

AMP-rated psychopathology in chronic alcoholics

Summary In a group of 39 alcoholics within a withdrawal process, the psychical situation was rated using AMP scales (Angst et al. 1969). Cluster analysis of the items rendered the following five-cluster solution: (1) aggressive-depressive patients, (2) less impaired persons, (3) slowed persons with diminished contact, (4) emotionally inadequate persons, (5) appealing depressive persons. These results are discussed with respect to other data from clinical history and diagnostic findings.Supported by Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 115, Teilprojekt C21     

A disease-specific psychosocial questionnaire for Parkinson’s disease caregivers

Abstract. Objective: To evaluate the Belastungsfragebogen Parkinson Angehörigen—kurzversion (BELA-A-k), a questionnaire for measuring psychosocial problems and need for help in Parkinsons disease (PD) caregivers. Methods: The Belastungsfragebogen Parkinson Angehörigen—kurzversion was translated into Dutch. It consists of 15 items with a Bothered by (Bb) and a Need for Help (NfH) score. The BELA-A-k was tested for cultural differences, relevance and feasibility in a pilot (n = 10). We determined the psychometric properties in a validation study (n = 50) and compared the BELA-A-k with the Sickness Impact Profile, the COOP/WONCA Functional Health Assessment Charts and the Loneliness Questionnaire (de Jong-Gierveld). All questionnaires were administered in person at home, in a prescribed order. Results: The BELA-A-k was completed by 60 PD-caregivers. The internal-consistency reliability coefficients for the total Bothered by (0.90) and Need for Help (0.92) scales were excellent. The internal consistency of the subscales exceeded the 0.70 standard except for the Bothered by and Need for Help Social functioning scale (Bb = 0.62; NfH = 0.65) and the Partner-bonding/Family scale (NfH = 0.69). Almost all BELA-A-k subscales correlated highly (P < 0.001) with the corresponding scales of the standard quality of life indices. Conclusion: The BELA-A-k is a relevant, reliable and valid measure for assessing psychosocial problems and need for help of PDcaregivers.     

The inflammatory lesion of T cell line transferred experimental autoimmune encephalomyelitis of the Lewis rat: distinct nature of parenchymal and perivascular infiltrates

We have investigated the T cell receptor (TCR) repertoire in the inflammatory infiltrates of T line-transferred experimental autoimmune encephalomyelitis (EAE) of the Lewis rats. Using a panel of TCR V-specific monoclonal antibodies (mAbs) and immunocytochemistry, we studied the nature of the T cells entering the central nervous system (CNS) after transfer of either myelin basic protein (MBP)-reactive, or MBP-reactive but non-encephalitogenic T cell lines. All the MBP-specific T cell lines predominantely used the V8.2 TCR chain. T cell lines specific for the tuberculin purified protein derivative (PPD), using TCR V genes different from V8.2, served as controls. We first studied the time course of T cells entering the CNS. In all recipient rats, small, but significant numbers of -TCR-expressing infiltrate cells appeared in the CNS within the first 24 h after T cell transfer. In animals injected with either type of MBP-reactive T cells, the early infiltrate cells were preferentially located within the parenchyma of the spinal cord, while in PPD T lineinjected rats, the lymphocytes were mostly found in the meninges. TCR V gene usage was examined on the peak of clinical disease. Six days after T cell transfer, the TCR repertoire used by infiltrating lymphocytes in general seemed to be highly diverse. None of the V isotypes examined (i.e. V8.2, V8.5 or V10) was used by a major population of the -TCR-positive T cells. A more detailed, quantitative analysis of individual infiltrate compartments revealed, however, a preferential accumulation of V8.2-positive T cells within the parenchyma. In contrast, perivascular infiltrating cells used V genes randomly. Our results confirm first that activated T lymphocytes enter the brain rapidly irrespective of their antigen specificity. Second, the data show that most of the perivascular infiltrate T cells in the acute EAE lesion are host-derived, recruited presumably from the recirculating T cell pool, while the encephalitogenic, V8.2-positive T cells preferentially persist within the parenchyma.Abbreviations EAE experimental autoimmune encephalomyelitis - MBP myelin basic protein - TCL T cell line Supported by the Brazilian Research Council (CNPq)     

Clinical and Human Resource Planning for the Downsizing of Psychiatric Hospitals: The British Columbia Experience

Riverview Hospital, B.C.'s only and Canada's largest remaining provincial psychiatric hospital began a formal planned downsizing process in 1992. This initiative was an important element in the Province's strategic plan to shift to a more community-focused mental health system and to bring tertiary psychiatric services closer to home by redeveloping Riverview Hospital on three sites. The paper summarizes the literature pertaining to the downsizing of psychiatric hospital services in relation both to clinical and human resource planning. It describes the mental health system in B.C. and the service system context in which this exercise is occurring. It is based on the first three years of experience in identifying the major challenges and the strategies developed to meet these challenges. It draws some conclusions about the effectiveness of these strategies and it speculates about the likely future challenges as the downsizing process continues.     

GABA binding sites: their density,their affinity to muscimol and their behaviour against neuroactive steroids in human gliomas of different degrees of malignancy

Summary The aim of the present investigation was to answer the question if there exists a relation between the equipment of human gliomas with GABA binding sites and the degree of malignancy of these tumours diagnostically characterized according to WHO classification. The following parameters were assessed: the density, the affinity and the sensitivity to the modulating steroids 3 -hydroxy-5 -pregnane-20-one (3 OH-DHP) and 3 ,21dihydroxy-5 -pregnane-20-one (THDOC). Scatchard analysis and non linear computerization revealed that the occurrence of GABA sites was directly related to the degree of tumour malignancy: GABA sites were only detectable in lower malignant gliomas of WHO grade II but not in the very malignant glioblastomas. However, irrespective of the individual density to be detected all glioma GABA sites were sensitive to 3 -hydroxy-5 -pregnane-20-one (3 OH-DHP) and 3 ,21dihydroxy-5 -pregnane-20-one (THDOC) without exception. The effects of THDOC were due to increases in the number of binding sites whereas in the presence of 3 OH-DHP a decrease in affinity was noted, additionally. These findings support the view of a normal functional integrity of GABA receptors in gliomas.     

Desynchronization of electrical activity in rats induced by deprenyl-an inhibitor of monoamine oxidase B- and relationship with selective increase of dopamine andβ-phenylethylamine

Summary Electrophysiological and biochemical effects of deprenyl and-phenylethylamine were studied in rats, d, l-Deprenyl, l-deprenyl (4–16 mg/kg) and-phenylethylamine (75 mg/kg) induced a desynchronization of ECoG after i.p. administration of drugs. The effects lasted several hours. The biochemical analysis indicate that d, l-deprenyl (4 mg/kg) nearly doubled the concentration of brain dopamine (DA) while the concentration of noradrenaline was not altered. The maximal increase was reached at 60 min and the enhanced concentration of DA stayed at this level up till 180 min after administration of drug. Treatment of rats with-methyl-p-tyrosine (200 mg/kg) did not antagonize a deprenyl induced desynchronization of ECoG. However, even low dose of haloperidol (0.1 mg/kg) abolished the arousal effect of d, l-deprenyl and-phenylethylamine. It is suggested that desynchronization of EEG induced by deprenyl is more likely due to increased endogenous-phenylethylamine than to increased concentration of endogenous DA in the brain.