Biomedical subjects

Tom G Bolwig

Publications and source records attributed to Tom G Bolwig.

27 records · Page 2Linked to original sources

PubMed2003

Role for M5 muscarinic acetylcholine receptors in cocaine addiction.

Muscarinic cholinergic receptors of the M5 subtype are expressed by dopamine-containing neurons of the ventral tegmentum. These M5 receptors modulate the activity of midbrain dopaminergic neurons, which play an important role in mediating reinforcing properties of abused psychostimulants like cocaine. The potential role of M5 receptors in the reinforcing effects of cocaine was investigated using M5 receptor-deficient mice in a model of acute cocaine self-administration. The M5-deficient mice self-administered cocaine at a significantly lower rate than wild-type controls. In the conditioned place preference procedure, a classic test for evaluating the rewarding properties of drugs, M5-deficient mice spent significantly less time in the cocaine-paired compartment than control mice. Moreover, the severity of the cocaine withdrawal syndrome (withdrawal-associated anxiety measured in the elevated plus-maze) was significantly attenuated in mice lacking the M5 receptor. These results demonstrate that M5 receptors play an important role in mediating both cocaine-associated reinforcement and withdrawal.

Animals↗

PubMed2003

Putative common pathways in therapeutic brain stimulation for affective disorders.

Brain stimulation methods in the treatment of affective disorder are electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS). Clinically, ECT is considered the strongest remedy in the treatment of severe depression, especially depression with psychotic features, and in the elderly. TMS, despite positive reports, is somewhat more controversial. VNS has, so far, only been used in treatment-resistant depression with limited results. DBS may be of potential use in rare cases of treatment-resistant cases of affective disorder. This article highlights the similarities and differences between the four stimulation methods. The main difference is the seizures necessary in ECT. A stronger involvement of the hippocampus following experimental seizures compared with effects in that region induced by TMS and VNS might explain the consistent findings of the superiority of ECT in the most severe cases of affective disorder.

Animals↗

PubMed2003

Quantitative electroencephalography in OCD patients treated with paroxetine.

The effectiveness of drugs that have a specific effect on the activity of the serotonergic neurotransmitter systemhas changed the outlook for patients suffering from obsessive-compulsive disorder (OCD). With a response rate of about 70% to such compounds and the great amount of brain imaging studies conducted over the past decades, an understanding of the biochemical nature and origins of OCD is beginning to unfold. Convergent data including ethological and experimental observations, clinico-pathological findings and different imaging methods have implicated the basal ganglia along with the cortical and related thalamic structures to be involved in the pathophysiology of OCD. In a previous study using the quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, two subtypes within a clinically homogeneous patient group were classified. Patients with relative excess theta activity, especially in the frontal regions, were nonresponders to treatment with serotonin reuptake inhibitors (SSRI), while those with increased relative power in alpha activity were responders to pharmacological treatment. These findings suggested at least two subgroups in a patient population with similar symptoms but differential responses to treatment. In the present study we used neurometric QEEG to subtype a group of 20 non-depressed OCD patients, fulfilling DSM-R-III criteria, treated with paroxetine, of whom 18 were responders to treatment. Of the treatment responders, 94.4% were predicted by subtype membership to be SSRI responsers. In these subjects there was a strong relative alpha baseline activity; after successful treatment through at least 3 months this activity decreased, looking more normal. The group average topographic maps showed none of the characteristics seen in the nonresponder cluster (no excess relative power in theta). As in the previous investigation, baseline QEEG profile membership points to a predictive value with regard to therapeutic response.

Adult↗

PubMed2002

[The effect of psychotherapy on depression].

Over the last decades, numerous studies of the efficacy of psychotherapy on major depression have been carried out. They provide evidence of the effectiveness of cognitive therapy and interpersonal therapy in the treatment of mild to moderate depression. The effectiveness of psychotherapy in in-patients and patients with severe depression has not been documented. Maintenance interpersonal therapy may contribute to prevent new episodes in recurrently depressive patients, where promising studies also indicate that cognitive therapy has a preventive effect on future depressions. This calls for larger and better controlled studies.

Depression↗

PubMed2002

[Electroconvulsive therapy in Denmark 1999. A nation-wide questionnaire study].

INTRODUCTION: The use of ECT in Denmark has not been systematically evaluated since 1979. Many changes have since taken place in the organisation of psychiatric care and the number of new drugs for the treatment of affective disorders has grown. We wanted to see whether the frequency of treatments and the technical standard of ECT had undergone changes in the same period. MATERIAL AND METHODS: A questionnaire was sent to all psychiatric departments in Denmark concerning the number of ECT sessions and ECT patients in 1999, and technical aspects and organisation of this treatment-modality. RESULTS: The percentage of replies was 100, all departments used ECT, and 86% of the departments adequately reported the number of ECT sessions and ECT-treated patients. The total number of sessions and patients treated was estimated from these answers. We found that the number of ECT sessions had fallen from 19,564 in 1979 to 16,306 in 1999 and the number of ECT patients from 2,332 in 1979 to 1,710 in 1999. ECT is thus given to an average of 5% of all hospitalised psychiatric patients. The number of sessions per patient had increased slightly. The technical quality of treatment with regard to the ECT devices used had improved considerably during the period. DISCUSSION: The use of ECT in Denmark shows a decline since the last evaluation in 1979. However, it still plays an important role in the treatment of hospitalised patients with depression in Denmark.

Denmark↗

PubMed2002

Extracellular levels of NPY in the dorsal hippocampus of freely moving rats are markedly elevated following a single electroconvulsive stimulation, irrespective of anticonvulsive Y1 receptor blockade.

Neuropeptide Y (NPY) has been proposed to play a role in the pathophysiology of depression and also to act as an endogenous anticonvulsant. Repeated administration of electroconvulsive stimulations (ECS) has been shown to induce a long-term increase in hippocampal NPY neurotransmission, while the effects of single ECS are largely unexplored. In this study, we assessed extracellular levels of NPY in the dorsal hippocampus of freely moving rats following a single ECS. We also studied the effect of locally administered BIBP3226, a selective NPY Y1 receptor antagonist with reported anticonvulsant properties, on the duration of the ECS-induced seizure and NPY release in freely moving animals. Our data demonstrate that a single ECS increases extracellular NPY-like immunoreactivity (LI) levels in the dorsal hippocampus, reaching statistical significance 2h following the treatment. KCl transiently and calcium-dependently increased extracellular levels of NPY, suggesting that the measured NPY-LI is derived from functional neurons. Local BIBP3226 perfusion essentially abolished the ECS-induced seizure but had no effect on the basal NPY-LI outflow or on the ECS-induced rise in extracellular NPY levels. Our data are in line with the hypothesis that one mechanism of action of ECS is to release NPY in the hippocampus and suggest that the increase is in itself not associated with anticonvulsant activity but may represent other properties of NPY.

Animals↗

PubMed2002

The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study.

Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD.

Adult↗

PubMed2002

Major depressive disorder in Parkinson's disease: a register-based study.

OBJECTIVE: To investigate whether patients with Parkinson's disease (PD) were at an increased risk of developing major depression compared with patients having other medical illnesses with a comparable degree of disability. METHOD: Case register linkage study of Danish Psychiatric Central Register (DPCR)and Danish National Hospital Register (DNHR). Three study cohorts were identified: all patients with PD, osteoarthritis, and diabetes. The rate of discharge diagnosis of depression on re-admission was estimated using competing risks models in survival analyses. The rates for patients with PD were compared with those of patients with osteoarthritis, and diabetes. RESULTS: The study sample identified 211 245 patients in the hospital registers with one of the index diagnoses. An increased incidence of developing depression was found for women and men throughout their lifetime when this incidence was compared with the control groups. CONCLUSION: The findings support the hypothesis that depression in patients with PD is a consequence of brain dysfunction.

Adult↗

PubMedDate not supplied

Ethanol withdrawal in rats is attenuated by intracerebroventricular administration of neuropeptide Y.

AIMS: The effects of intracerebroventricular administration of neuropeptide Y (NPY) on ethanol withdrawal were studied in rats. METHODS: Ethanol was administered intragastrically five times daily for 4 days. At 16-17 h after the last infusion of ethanol, rats were rated for withdrawal using a score based on three signs: irritability, tremor and rigidity. Subsequently, the rats received an injection of NPY (12 or 24 nmol) or vehicle and were rated for signs of withdrawal. RESULTS: At both doses, NPY significantly reduced ethanol withdrawal, the effect of the larger dose being more pronounced. CONCLUSIONS: Our results are consistent with the concept that NPY receptors are centrally involved in the regulation of neuronal excitability and might form a novel therapeutic target for treatment of ethanol withdrawal and other states of neuronal hyperexcitability.

Animals↗