Biomedical subjects

Markus Heilig

Publications and source records attributed to Markus Heilig.

41 records · Page 3Linked to original sources

PubMed2002

Anxiogenic-like action of centrally administered glucagon-like peptide-1 in a punished drinking test.

A role for glucagon-like peptide-1 (GLP-1) has been postulated in the regulation of blood glucose and satiety. In addition, intracerebroventricular administration of GLP-1 has been shown to suppress locomotor activity, and produce a neuronal activation in the amygdala, a structure involved in mechanisms of fear and anxiety. Adult male Sprague-Dawley rats were prepared with chronic intracerebroventricular cannulae. Measures of experimental anxiety were assessed by the Vogel conflict test and the elevated plus maze. Central GLP-1 (fragment 7-36) administration produces a proconflict effect in the punished drinking test, while leaving measures of activity and nociception unaffected. GLP-1 may participate in the control of fear-induced suppression of behavior, probably via action in the amygdala.

Amygdala↗

PubMed2002

The dual-diagnosis concept used by Swedish social workers: limited validity upon examination using a structured diagnostic approach.

A co-existence of chemical dependence and other psychiatric syndromes is commonly referred to as "dual-diagnosis." This categorization is commonly made by social workers in several European countries assigned the primary responsibility for the care of drug and alcohol dependence. Here, we examined the validity of this categorization through systematic, structured patient evaluation following a minimum of 3 weeks of abstinence from drugs and alcohol. Less than one-third of patients originally labelled as suffering from "dual-diagnosis" by the social services did in fact obtain any Axis I DSM IIIR diagnosis, and less than half of the patients had any psychiatric diagnosis other than dependence. Syndromes commonly discussed in the context of self-medication, i.e., unipolar depression and anxiety syndromes, were not over-represented compared to a population sample, while chronic psychoses and bipolar syndromes were highly significantly more common. We conclude that the dual-diagnosis concept, unless substantiated through stringent diagnostic procedures by psychiatrically trained personnel, may be of questionable utility in caring for patients presenting with psychiatric symptoms and substance dependence. A systematic individual evaluation in an alcohol- and drug-free state of sufficient duration is necessary to obtain a basis for an adequate individual treatment plan.

Adult↗

PubMed2002

Long-lasting increase in voluntary ethanol consumption and transcriptional regulation in the rat brain after intermittent exposure to alcohol.

Prolonged exposure of the brain to ethanol is a prerequisite for developing ethanol dependence, but the underlying neural adaptations are unknown. Here we demonstrate that rats subjected to repeated cycles of intoxication and withdrawal develop a marked and long-lasting increase in voluntary ethanol intake. Exposure-induced but not spontaneous alcohol intake is antagonized by acamprosate, a compound clinically effective in human alcoholism. Expression analysis of cingulate cortex and amygdala reveals a set of long-term up-regulated transcripts in this model. These include members of pathways previously implicated in alcohol dependence (glutamatergic, endocannabinoid, and monoaminergic neurotransmission), as well as pathways not previously thought to be involved in this disorder (e.g., members of the mitogen-activated protein kinase pathway). Thus, alternating periods of ethanol intoxication and withdrawal are sufficient to induce an altered functional brain state, which is likely to be encoded by long-term changes in gene expression. These observations may have important implications for how alcoholism is managed clinically. Novel clinically effective treatments may be possible to develop by targeting the products of genes found to be regulated in our model.

Acamprosate↗

PubMed2002

Brain neuropeptide Y (NPY) in stress and alcohol dependence.

Neuropeptide Y (NPY), the prototypical member of the NPY-like peptide family, antagonizes behavioral consequences of stress through actions within the brain. This was initially indicated by microinjection studies with NPY receptor ligands, suggesting that NPY Y1 receptors mediate the anti-stress effects of NPY. Behavioral anti-stress actions of NPY are note-worthy in that 1) their magnitude surpasses that of other endogenous compounds; 2) they are produced across a wide range of animal models, normally thought to reflect different aspects of emotionality. These findings suggest that NPY acts with a high potency on a common core mechanism of emotionality and behavioral stress responses. This hypothesis is supported by behavioral studies in genetically modified animals. Increased emotionality, as well as increased alcohol intake, has been reported in mice with a homologous recombination knockout of the preproNPY gene. More detailed studies have been made possible by a transgenic rat system, in which NPY is selectively overexpressed within the hippocampus. These subjects display no overt phenotype under baseline conditions and have a normal endocrine stress response, but lack behavioral responses to stress. These findings point to the potential of the NPY system for developing novel pharmacological treatments of stress-related disorders, including anxiety and depression. Recent data additionally point to a role of NPY in the regulation of alcohol intake, and alcohol dependence emerges as a novel potential indication for compounds targeting the NPY system.

Alcoholism↗

PubMedDate not supplied

Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism.

Extensive animal studies suggest neuropeptide Y (NPY) to be involved in coping with a wide range of stressors, and that impaired central NPY signalling could be involved in the pathophysiology of anxiety and depression. Human studies of central NPY levels in depression have, however, been inconclusive. Here, we examined levels of NPY-like immunoreactivity (NPY-LI) in the cerebrospinal fluid (CSF) of medication-free subjects with treatment refractory unipolar depression. Patients were admitted to a research inpatient unit, examined under standardized conditions, and compared with a sample of volunteers in whom psychiatric morbidity was excluded. A robust suppression of NPY levels in patient CSF was found, while other putative CSF markers (monoamine metabolites, somatostatin) did not differ between the groups. We then explored whether this finding might be related to a recently described T1128C coding polymorphism which results in a Leu7-> Pro7 substitution of the signal peptide, and a previously not described T -399C polymorphism in the promoter region of the preproNPY gene. Preliminary evidence was found for an association of both markers with a diagnosis of depression, indicating the possibility of an underlying haplotype influencing the vulnerability for developing depressive illness. Our present findings are in line with an extensive animal literature, and further support the notion that impaired NPY function could contribute to depressive illness.

Adult↗