Biomedical subjects

Markus Storvik

Publications and source records attributed to Markus Storvik.

4 recordsLinked to original sources

PubMed2006

Lower serotonin transporter binding in caudate in alcoholics.

Dorsal striatum is regulated by the serotonergic system, and it is a brain area with a role in the development of obsessive thought patterns, which may be related to addiction. In this study, possible alterations of [(3)H]citalopram binding to serotonin transporter (SERT) were evaluated in the dorsal striatum of Cloninger type 1 and 2 alcoholics, and nonalcoholic control subjects by postmortem whole-hemisphere autoradiography in humans. The SERT binding was significantly lower (-26%, effect size 1.74) in the caudate body of alcoholics. The SERT binding tended to be lower also in the other parts of the dorsal striatum in alcoholics, but the results did not reach significance. In addition, there was a significant positive correlation, especially in type 1 alcoholics, between the SERT binding in the body of the caudate and in the perigenual anterior cingulate cortex, an area in which the SERT binding has been shown to be lower among alcoholics. These results give preliminary evidence to suggest that the SERT binding in the dorsal striatum may be lower in alcoholics, and that the serotonergic system may be affected in cortical and striatal areas simultaneously. The cortico-striatal-thalamic axis may have an important role in fully developed addictions and the characterization of these correlations within the serotonergic system may lead to a better understanding of the anatomical dynamics underlying the neurochemistry of alcoholism.

Alcoholism↗

PubMed2005

Distinct gene expression profiles in adult rat brains after acute MK-801 and cocaine treatments.

Uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists have been suggested to attenuate the self-administration and rewarding effects of psychostimulants. Microarrays containing 14,500 rat cDNAs were hybridized to identify alterations in gene expression levels in rat brain regions elicited by the uncompetitive NMDA receptor antagonist MK-801 (dizocilpine, 1 mg/kg), the dopamine agonist cocaine (20 mg/kg), or combined treatment (MK-801 15 min prior to cocaine) 4 h after injections. Total genes up regulated (Z-ratio >2) in parietal cortex and nucleus accumbens were 111 and 158, respectively. Total genes down regulated (Z-ratio <2) in the same tissues were 360 and 166, respectively. These genes fell into multiple molecular function gene ontology (GO) categories, but were highly represented in catalytic activities (44% of all genes), signal transduction (14%), protein (20%), nucleotide (18%), and nucleic acid (15%) binding. In nucleus accumbens, genes up regulated by MK-801 (87 genes) did not overlap those up regulated by cocaine (46 genes). Genes down regulated by MK-801 (33 genes) consisted of 2 overlapping genes with those down regulated by cocaine (89 genes). In parietal cortex, low numbers of overlapping regulated genes were also observed. Combined treatments also indicated low numbers (0-10) of genes commonly regulated when compared with single treatments alone. In situ hybridisation studies indicated significant increases in b-ZIP transcription factors (CREM, ICER, CBP, and c-fos) elicited by MK-801 and decreases in c-fos elicited by cocaine. The results indicate independent gene expression signatures following acute MK-801 and cocaine administration that appears to be largely non-overlapping and context dependent.

Animals↗

PubMed2005

Seasonal variations in [3H]citalopram platelet binding between healthy controls and violent offenders in Finland.

Monthly binding densities (B(max)) of [3H]citalopram to the platelet serotonin transporter (SERT) was measured longitudinally over 1 year in a control group of 18 healthy Finnish male volunteers. Single platelet samples were also analysed from 33 men who were incarcerated for violent crimes during the same calendar year. A statistically significant seasonal variation in SERT B(max) was observed in both data sets, and bi-monthly floating averages for SERT B(max) were calculated and then fit to an annual sinusoidal curve for both groups. The B(max) for platelet [3H]citalopram binding showed a statistically significant (p = 0.001) seasonal variance between a winter (January-February) maximum of 1590 fmol/mg protein and a summer (July-August) minimum of 1216 fmol/mg protein for the control group, with an R2 of 70% for the annual sinusoidal curve fit. A statistically significant (p = 0.007) seasonal variance was also observed between a winter (January-February) maximum of 1980 fmol/mg protein and an autumnal (August-September) minimum of 1234 fmol/mg protein for the violent offenders, again with an R2 of 70% for the annual sinusoidal curve fit. This observation lends additional support to the idea that violent human behavior and impulsivity may be directly linked to values of SERT B(max), which can be affected by various psychoactive drugs and also varies with the natural change of seasons.

Adult↗

PubMed2003

Subunit selective decrease of AMPA and metabotropic glutamate receptor mRNA expression in rat brain by systemic administration of the NMDA receptor blocker MK-801.

Glutamate mediates its effects in mammals through both ionotropic and metabotropic receptors. Antagonists of ionotropic N-methyl-D-aspartate (NMDA) glutamate receptors elicit neuroprotective and neurotropic effects that have been attributed to Ca2+ block through the membrane ion channel. Nonetheless, molecular and biochemical effects of NMDA receptor antagonism on other glutamate receptor subunits remain poorly understood. We investigated the effects of acute administration of the noncompetitive NMDA receptor antagonist MK-801 on the mRNA expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and metabotropic glutamate receptor (mGluR) subunits to determine the contribution of different glutamate receptors in response to blockade of NMDA receptor channels. In situ hybridization to rat brain sections revealed that AMPAreceptor subunits GluR3 and GluR4, and mGluR3 were modestly but significantly decreased approximately 10-20%, 8 h following 5 mg/kg MK-801 administration. Atime course and dose response study revealed that the effect on mGluR3 was reversed by 24 h and occurred significantly at a dose range from 1 to 5 mg/kg. These results indicate that selected AMPA and mGluR subunit mRNAs respond at the RNA level to the blockade of NMDA receptors.

Animals↗