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Biomedical subjects

T G Bolwig

Publications and source records attributed to T G Bolwig.

At least 73 records · Page 4Linked to original sources
PubMed1993

Effects of chronic discontinuous and continuous treatment of rats with a dopamine D1 receptor antagonist (NNC-756).

Rats were treated intermittently or continuously with the dopamine D1 receptor antagonist NNC-756 for 15 weeks. Two weeks after withdrawal they were challenged with the dopamine D1 receptor agonist SK&F 38393, either alone or after pretreatment with NNC-756. Neither treatment regimen resulted in irreversible increases in oral activities when treated rats were compared with controls; however, transient elevations were observed in the beginning of treatment in the continuously treated group and in the withdrawal phase in the discontinuously treated group. Furthermore, discontinuous treatment resulted in within-group elevations in vacuous chewing movements and tongue protrusions after withdrawal. Dopamine D1 receptor supersensitivity was not observed after challenge with the dopamine D1 receptor agonist. NNC-756 efficiently blocked the behavioural response to stimulation with SK&F 38393. Both treatment regimens resulted in the development of rigidity and catalepsy. The present study suggests that treatment with selective dopamine D1 receptor antagonists is less likely to cause irreversible oral dyskinesia than is treatment with classical neuroleptic drugs.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Electrical kindling of rats treated discontinuously or continuously with haloperidol.

Intermittent as opposed to continuous treatment of rats with haloperidol resulted in a long-lasting potentiation of oral activity. To examine if this behavioural sensitization to discontinuous neuroleptic treatment facilitates seizure development in electrical kindling, rats treated either intermittently or continuously with haloperidol for 15 weeks were kindled in the nucleus amygdala. Development of kindled seizures was significantly faster in the intermittently treated group (P < 0.01) than in controls or continuously treated rats. Furthermore, discontinuously treated animals displayed electroencephalographic afterdischarges in the substantia nigra from the beginning of treatment. The findings of cross-sensitivity between electrical amygdala kindling and pharmacological sensitization and of early appearance of epileptiform nigral activity have implications for the pathogenesis of both conditions. We suggest that depressed gamma-aminobutyric acid activity in substantia nigra could be a common mechanism.

Amygdala↗
PubMed1993

Therapeutic potentials of recently introduced antidepressants. Danish University Antidepressant Group.

The DUAG studies showed that in well-designed and rigorously executed multisite drug trials three representatives (citalopram, paroxetine, and moclobemide) from two classes of recent antidepressant drugs were less effective than the standard reference drug, clomipramine. The most important reasons for the superiority of clomipramine was probably that clomipramine was given in a high and fixed dose of 150 mg per day throughout the entire treatment period and that patient compliance was ensured through drug monitoring. When the DUAG studies are compared with "no difference" studies, the difference between DUAG and others lies not so much in a different efficacy of the test drugs but in the efficacy of the reference drugs, where clomipramine in the DUAG studies was more effective than reference tricyclics in most other studies with flexible dose regimens. A relatively high rate of adverse drug reactions with clomipramine administered in high and fixed doses was probably due to a considerable interindividual variability in the pharmacokinetic properties. (Gram 1990), and the development of side effects may be predicted and prevented when better knowledge of plasma concentration and dose-response relations for classical tricyclic antidepressants allow individual dose adjustments. Such studies are under way with in the DUAG. The results of such studies may reduce the need for new antidepressants which, although less toxic than the classical tricyclics, may prove to be also less potent. The DUAG studies were performed in hospitalized, moderately to severely, endogeneously depressed adult patients and conclusions from the DUAG studies about the superiority of clomipramine over three recent antidepressants cannot readily be generalized to cover less homogeneous groups of outpatients with milder depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Antidepressive Agents↗
PubMed1993

Seizure threshold to lidocaine is decreased following repeated ECS (electroconvulsive shock).

Seizure susceptibility to lidocaine was investigated in rats which had received repeated ECS (electroconvulsive shock). In the first experiment three groups of rats received an ECS daily for 18 days, an ECS weekly for 18 weeks, and 18 sham treatments, respectively. Twelve weeks after the last ECS all rats received a lidocaine challenge (LC) in the form of an intraperitoneal (IP) injection of lidocaine (65 mg/kg). After the injection the animals were observed for occurrence of motor seizures. A total of 67% (10/15), 47% (7/15), and 0% (0/18) of the daily, weekly, and sham groups, respectively, had motor seizures in response to the LC. In the second experiment five groups of rats received an ECS daily for 0, 1, 6, 18, and 36 days, respectively. Eighteen weeks after the last ECS all rats received an LC and 0% (0/15), 13% (2/15), 20% (3/15), 53% (8/15), and 58% (7/12), respectively, developed seizures in response to the LC. In the third experiment two groups of rats received daily ECS and sham-ECS, respectively. Twenty-four hours after the last ECS all rats received an LC. A total of 60% (9/15) of the ECS group and 0% (0/10) of the sham-ECS group had seizures in response to the LC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Electroconvulsive shock (ECS) does not facilitate the development of kindling.

UNLABELLED: 1. For many years it has been discussed whether repeated electroconvulsive shock (ECS) may induce a lasting epileptogenic effect on the brain (i.e. a kindling effect). In the present study the authors investigated whether weekly ECS do exert such an effect. 2. Bipolar electrodes were implanted in amygdala of 32 rats. Following a two to three week recovery period the rats were randomly allocated to two groups. One group received 12 weekly ECS, the other 12 weekly sham-ECS. 3. Three months after the last ECS/sham-ECS, kindling was initiated. Daily stimulation, eliciting an EEG-afterdischarge was given to all the rats. The animals received a total of 15 stimulations. 4. ECS-pretreated animals did not kindle faster than the sham-group. The two groups reached stage 4 (clonic rearing) after 5.8 (ECS-group) and 5.7 (sham-group) stimulations, respectively. 5. The authors did not find a facilitated development of kindling following ECS, instead they observed a slight, yet statistically significant inhibition of the development of the maximally generalized kindling-seizure--the stage 5 seizure--in the ECS-group. 6. IN CONCLUSION: The present study did not show a kindling effect of weekly ECS suggesting that kindling requires more than repeated elicitation of after-discharge.

Amygdala↗
PubMed1993

Regional cerebral blood flow in affective disorder.

The results of two-dimensional cerebral blood flow (CBF) studies in depression and the results of measurements of regional CBF (rCBF) using single photon emission computerized tomography (SPECT) are briefly reviewed. A technical outline of both types of method is described. The majority of SPECT studies point to a decreased CBF in untreated patients with a tendency towards normalization, but other studies suggest that, following treatment, there is an increase above normal either from a decreased or an abnormally high initial level. One study has pointed to unipolar patients having lower flow in the right temporal and parietal lobes relative to normals, whereas non-endogenous patients did not differ significantly from normal controls. Bipolar depressives have been found to have higher flow values than normals in the parietal and temporal lobes in the left hemispheres. This relevant aspect or a possible relationship between type of depression and hemispheric asymmetry needs further study for full classification. Thus, most investigations designed to determine which brain structures might be involved in regulating affect have not been very successful, which may be a consequence of the biological heterogeneity of these disorders or of the limited spatial resolution of the techniques used for investigation. Even if some of these technical difficulties can be overcome with measurements of receptor kinetics supplemented, other biological variables that have proved valuable in psychiatry (such as rapid eye movement latency and biogenic amines) should be studied to find more precise biological markers for depressive illness.

Cerebrovascular Circulation↗
PubMed1993

A study of psychiatric morbidity in patients with Huntington's disease, their relatives, and controls. Admissions to psychiatric hospitals in Denmark from 1969 to 1991.

Psychiatric morbidity among 74 non-affected first-degree relatives and 93 non-affected second-degree relatives of patients with Huntington's disease (HD) was compared with that of 37 patients with HD and with matched control groups. Due to specific age criteria, the first-degree relatives were at decreased risk and the second-degree relatives at negligible risk of being carriers of the gene for HD. Information on admissions to departments of psychiatry and diagnoses at discharge were obtained for all subjects from a nationwide central register. Psychiatric morbidity was no greater among relatives than among controls, whereas HD patients had significantly more admissions and psychiatric diagnoses than relatives. Growing up with a risk of developing HD does not itself increase the risk of developing psychiatric illness resulting in hospital admission. Severe psychiatric disorders in HD patients were thus most likely to be aetiologically related to the disease process, possibly through a genetic mechanism.

Adult↗
PubMed1992

[Electric stimulation (ECT) in Parkinson disease].

A case report and a review of the literature concerning electroconvulsive therapy (ECT) in the treatment of Parkinson's disease with special reference to the therapy of "on-off" phenomena is given. The first report of positive effect appeared in 1959 and, with a single exception, all published articles on this topic point to a positive outcome of ECT. There seems to be a specific anti-Parkinsonian effect alongside the well-known effect on various psychotic conditions. ECT thus must be considered a valuable intervention when drug therapy is insufficient, when prolonged medication leads to decreased efficacy, or when patients develop neuro-psychiatric manifestations. A short review of the pathophysiological mechanisms which may underly the effect of ECT in Parkinson's disease is given.

Electroconvulsive Therapy↗
PubMed1992

Kidney functioning during lithium treatment: a prospective study of patients treated with lithium for up to ten years.

A cohort of 53 patients with affective disorders who originally carried through renal functional tests before start of prophylactic lithium treatment were followed up prospectively after an average period of 8.5 years (range 7-10 years). Ten patients who had continued lithium treatment were re-examined. In this subgroup, the glomerular function was unaffected by the treatment, whereas the average urine volume increased during lithium treatment (NS). Polyuria and low renal concentrating abilities were also found before start of treatment and these findings underline the importance of access to renal baseline information prior to lithium treatment.

Adult↗
PubMed1991

Hippocampal kindling in the rat is associated with time-dependent increases in the concentration of glial fibrillary acidic protein.

The effect of hippocampal kindling on the regional brain concentration of total glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, was studied in partially kindled rats, and in fully kindled rats after a post-kindling period of 24 h, 1 week, and 2 months. GFAP concentration was measured in arbitrary units by dot-blots. In the hippocampus, dentate gyrus, basolateral amygdala, pyriform cortex, and entorhinal cortex, limbic structures which are known to be involved in the kindling process, there was an increase in GFAP concentration which was maximal in the fully kindled animals studied after 24 h. In most brain areas, GFAP concentration was still elevated 1 week post-kindling, but had declined to control level 2 months post-kindling. A significant increase in GFAP was also found in septum, ventral pallidum/accumbens nucleus, and primary motor cortex of kindled rats with a post-kindling period of 24 h, whereas in several other brain regions GFAP was unchanged. These results suggest that astrocyte activation, indicative of degenerative changes in nearby neurons, is a transient and regional phenomenon in kindling occurring only during the development of the kindled state.

Animals↗
PubMed1991

Lithium: long-term effects on the kidney. A prospective follow-up study ten years after kidney biopsy.

Forty-six patients with recurrent affective disorders, who began prophylactic treatment with lithium an average of 20 years previously, were followed up prospectively after a ten-year observation period to assess renal function. Nineteen patients had maintained lithium therapy, and eight patients had died. Tubular function was almost unchanged and patients who had continued lithium had not shown increasing urine volumes, but patients who had received lithium in a single daily dosage at night had a significantly lower urinary output than those on a multiple-dosage schedule. The GFR decreased significantly, but the decline was essentially dependent on increasing age, except in two patients who had developed renal insufficiency. Renal function during chronic lithium treatment is related to age, lithium intoxication episodes, pre-existing renal disease, and treatment schedule rather than to duration of prophylactic lithium therapy.

Adult↗
PubMed1990

Intermittent versus continuous neuroleptic treatment in a rat model.

The treatment schedule for neuroleptic therapy is of relevance when evaluating the development of side-effects. Seventy-five rats were treated discontinuously or continuously with the predominantly dopamine D2 receptor blocker haloperidol or the combined dopamine D1/D2 receptor blocker zuclopenthixol for 15 weeks. During and after treatment, a broad spectrum of behavioural parameters including vacuous chewing movements and tongue protrusions were observed. Discontinuous neuroleptic treatment as opposed to continuous neuroleptic treatment produced a significant long-lasting increase in oral activity. The changes were most pronounced in haloperidol-treated rats. The differences observed may have methodological implications for animal models of neuroleptic-induced movement disorders. Our findings are consistent with the hypothesis that pharmacological sensitization to the dyskinetic side-effects of neuroleptics develops when the drug effect is allowed to wear off between repeated administrations.

Animals↗
PubMed1990

Hippocampal kindling alters the concentration of glial fibrillary acidic protein and other marker proteins in rat brain.

The effect of hippocampal kindling on neuronal and glial marker proteins was studied in the rat by immunochemical methods. In hippocampus, pyriform cortex and amygdala there was an increase in glial fibrillary acidic protein (GFAP), indicating reactive gliosis, and an increase in the glycolytic enzyme NSE, suggesting increased anaerobic metabolism. Neuronal cell adhesion molecule (NCAM) decreased in pyriform cortex and amygdala of kindled rats, indicating neuronal degeneration.

Animals↗
PubMed1989

Grafts of fetal locus coeruleus neurons in rat amygdala-piriform cortex suppress seizure development in hippocampal kindling.

Hippocampal kindling was investigated in rats with a 6-hydroxydopamine-induced lesion of the forebrain catecholamine system after implantation of neural tissue from the fetal locus coeruleus region either bilaterally into the amygdala-piriform cortex (i.e., distant to the kindling site) or unilaterally into the hippocampus (close to the kindling site). Lesioned animals with either sham grafts or control grafts consisting of fetal striatal tissue showed a kindling rate much faster than that of normal controls. In contrast, in rats with bilateral locus coeruleus grafts in the amygdala-piriform cortex (implanted at three sites) the development of seizures was similar to that of controls and significantly slower than that in lesioned animals with sham grafts. All these animals had bilateral surviving grafts with a mean of 125 noradrenergic cells per implantation site. In the animals with locus coeruleus grafts in the stimulated hippocampus the kindling rate did not differ from that in the lesioned animals with control grafts. Most of these animals had large surviving grafts and showed a dense noradrenergic reinnervation of the implanted hippocampus. The present findings indicate that grafting of fetal pontine tissue (rich in noradrenergic neurons) to a site distant to the stimulation focus, but important for the generalization and spread of seizures, can retard the development of seizures in hippocampal kindling. Together with the data of our previous report this study also indicates that noradrenergic reinnervation of both hippocampi is important for the seizure-suppressant action in hippocampal kindling of locus coeruleus grafts implanted in the hippocampus.

Amygdala↗