Biomedical subjects

Michael Lehofer

Publications and source records attributed to Michael Lehofer.

6 recordsLinked to original sources

PubMed2006

[35S]GTPgammaS binding at the human dopamine D4 receptor variants hD4.2, hD4.4 and hD4.7 following stimulation by dopamine, epinephrine and norepinephrine.

Aim of the present study was to investigate possible differences between the human dopamine D4 receptor 48 bp polymorphism variants hD4.2, hD.4. and hD4.7 in agonist stimulated [35S]GTPgammaS binding, to investigate dopamine D4 receptor sodium sensitivity and to further characterize norepinephrine and epinephrine agonism at this receptor. G-protein activation at the receptor variants hD4.2, hD4.4 and hD4.7 expressed in CHO-K1 cells, following stimulation by dopamine, norepinephrine and epinephrine, was investigated using the [35S]GTPgammaS assay at experimental conditions of 10 and 100 mM sodium, respectively. Dopamine displayed a 2 fold higher potency of stimulating [35S]GTPgammaS binding at the hD4.2, compared to the hD4.4 and hD4.7 at 10 mM sodium. A significant difference in sodium sensitivity of basal [35S]GTPgammaS binding was found, with the hD4.7 being 1.7 fold more sensitive than the hD4.4 and 2.5 fold more sensitive than the hD4.2. Norepinephrine and epinephrine both produced concentration-dependent increases in [35S]GTPgammaS binding at all three receptor variants, and epinephrine showed only 2 fold less potency than dopamine. The present results are in certain line with previous reports of functional 2-3 fold differences between the dopamine D4 receptor variants. Agonism of norepinephrine and epinephrine at the dopamine D4 receptor may indicate an important way of cross-reactivity among the different monoamine neurotransmitter systems.

Animals↗

PubMed2005

Test-retest reliability of a lifetime drug use questionnaire.

By adopting the investigational principle of the Lifetime Drinking History (LDH) interview, we developed a Lifetime Drug Use (LDU) Questionnaire to assess the amount and frequency of lifetime drug consumption. The Pearson Correlation Coefficients for test-retest reliability, investigated in a sample of N=47 residents of a drug rehabilitation center and averaged over the investigated seven drug categories, were r=.95 for the abstinence-corrected total duration of regular use, r=.89 for the mean number of consumption days per month of regular use, r=.89 for the mean daily amount, r=.83 for the variability in consumption days per month of regular use, and r=.75 for month variability in daily amount. Applicability and further research needs are discussed.

Adult↗

PubMed2005

[A systemic view on psychosis].

The experience of time changes during life. In the youth time changes slowly from the longitudinal point of view, looking cross on life very fast. In older ages regularly it is the opposite matter, although there are throughout all ages significant intra- and interindividually differences. Experience of time is highly sensitive towards changes of one's self-experience, which can be well observed in psychiatric disorders. In case of psychosis identity of time and experienced synchronism (as certainty to be in the time with others) will be destroyed. There is a kind of breaking up time, a compression of time, where there is no before nor after. In depressed people time experience is similar to elder people, accordingly manic patients feel something like children in this sense. Dissociation of time has got a key role for understanding psychosis from the systemic point of view. Synchrone dissociation is distinguished from diachrone dissociation. In the first case conflicts will be "solved" through excessive simultaneity, undercutting the minimal time interval. The possibilities of differences are made impossible. Secondly the maximum of the time interval is exceeded; therefore the integration of opposite aspects is impossible. Equally no conflict will be possible. Both kinds of dissociation lead to "pseudo-harmony" of interrelational systems, despite of potency for conflicts. In family systems with schizophrenic members synchrone dissociation is typical, whereas diachrone dissociation is common in those with affective disorders. Both of them will be found in communicative systems with patients suffering from schizoaffective disorders. In between occur fierce arguments, when "protection" of dissociation is not granted.

Affective Disorders, Psychotic↗

PubMed2004

Dopamine receptor D3 mRNA expression in human lymphocytes is negatively correlated with the personality trait of persistence.

It has been proposed that neurotransmitter receptor expression in peripheral immune cells reflects expression of these receptors in the brain. To test this "peripheral marker hypothesis", we compared mRNA expression of the dopamine receptors D3 (DRD3) and D4 (DRD4) in peripheral blood lymphocytes (PBL) to personality traits assessed with the Temperament and Character Inventory (TCI) in 50 healthy and unmedicated Caucasian individuals. A shared variance of at least 17% (p=0.016) between DRD3 mRNA expression in PBL and the personality trait of persistence was found. As personality traits have been generally assumed polygenic with a single gene accounting for rarely more than 1-2% of observed variance in a trait, this result lends further support to the peripheral marker hypothesis for DRD3 mRNA expression in PBL. It may also suggest a significant role for the DRD3 in the neurobiology of persistence and point to an interesting link between personality and functioning of the immune system.

Adult↗

PubMed2004

Reduced dopamine D3 receptor expression in blood lymphocytes of smokers is negatively correlated with daily number of smoked cigarettes: a peripheral correlate of dopaminergic alterations in smokers.

The mesolimbic dopaminergic system is known to mediate rewarding effects of nicotine administration, and dysfunctions of this system may underlie failure to stop cigarette smoking. Expression of dopamine receptors in peripheral blood lymphocytes (PBLs) has been indicated as a peripheral correlate of brain status. Dopamine receptor D(3) (DRD3) and D(4) (DRD4) mRNA expression in PBLs was measured by real-time polymerase chain reaction in smokers (n=26) and former smokers (n=14), compared with nonsmoking control subjects (n=35). A significant (p=.032, Bonferroni corrected) 30% reduction of DRD3 mRNA expression in PBLs was found in smokers but not former smokers in comparison with controls. DRD3 mRNA expression in PBLs in smokers but not former smokers was negatively correlated with daily number of cigarettes consumed (Pearson correlation coefficient r=-.54, p=.005). These data suggest a selective inhibiting effect of smoking on DRD3 mRNA expression and, with the known involvement of DRD3 in reward mediation, indicates a vicious-cycle explanation for the motivation for continued smoking.

Actins↗

PubMed2004

Reduced dopamine D4 receptor mRNA expression in lymphocytes of long-term abstinent alcohol and heroin addicts.

AIM: It has been repeatedly suggested that dopamine receptor expression in peripheral blood lymphocytes reflects, to some extent, brain status. The aim of the present study was to investigate dopamine receptor expression in peripheral blood lymphocytes of long-term abstinent alcohol and heroin addicts against the background of the hypothesis, that a persisting dysfunction of the dopaminergic system contributes a biological cause to the chronic character of addiction. DESIGN: Dopamine D3 and D4 receptor mRNA expression in peripheral blood lymphocytes was measured by real-time polymerase chain reaction (PCR) in 19 alcohol addicts, abstinent for 6.2 +/- 4.7 months (mean +/- SD), and 20 heroin addicts, abstinent for 6.7 +/- 3.7 months (mean +/- SD), and compared to a control group of 29 age- and sex-matched individuals with no life-time history of substance abuse. FINDINGS: One-way anova showed significant differences in D4 mRNA expression between the groups (P = 0.005): both groups of addicts showed an approximately 50% reduction in D4 receptor mRNA expression in peripheral blood lymphocytes (PBL) compared to controls. No differences were found for D3 mRNA expression between the groups. CONCLUSION: The results of the present study indicate a withdrawal-persisting dopaminergic imbalance in abstinent addicts as measured by a suggested peripheral marker.

Adult↗