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Biomedical subjects

Marek Siemiatkowski

Publications and source records attributed to Marek Siemiatkowski.

7 recordsLinked to original sources

Cycloheximide impairs acquisition but not extinction of cocaine self-administration.

The aim of the present study was to assess the role of de novo protein synthesis in the acquisition and extinction of cocaine self-administration. In a first experiment, rats were trained to respond for intravenous cocaine infusions (0.3 mg/kg) and a protein synthesis inhibitor, cycloheximide (CHX; 3 mg/kg, s.c.) was injected immediately after each self-administration session. In a second experiment, rats were allowed to acquire cocaine self-administration and CHX was injected immediately after subsequent extinction sessions. CHX impaired the acquisition, but not extinction, of cocaine self-administration. In control experiments, CHX (3 mg/kg) blocked c-Fos protein expression after foot-shock stress and impaired the acquisition of conditioned freezing but did not inhibit spontaneous locomotor activity and sucrose drinking. Our results suggest that: i) the acquisition and extinction of cocaine-reinforced behaviour have a different molecular basis; and ii) only the former process requires de novo protein synthesis.

Animals↗

Neophobia and cortical and subcortical binding of the dopamine D2 receptor antagonist [3H]-raclopride.

The potential role of dopamine system in response to novelty was analysed using the selective dopamine D2 receptor antagonist, raclopride, in behavioral and biochemical assays, in rats (the open field test, and specific binding of [3H]-raclopride, within different brain structures measured with autoradiography). It was found that raclopride at a low dose (50 microg/kg, IP) caused anxiolytic-like effect (increased the anti-thigmotactic index), whereas at a higher dose (500 microg/kg, IP) produced general inhibitory influence, and decreased the anti-thigmotactic index. Analysis of the behavioral and biochemical results of the experiment revealed a significant negative correlation between the ligand binding in the substantia nigra pars reticulata (SNR), and the number of entries into the central sector of the open field (r=-0.48, p<0.05), as well as the positive correlation between time spent in the central sector of the open field and [3H]-raclopride binding within nucleus accumbens septi (r=0.57, p<0.05). Factor analysis revealed a Factor 1 (eigenvalue=3.361) grouping parameters of central entries into the open field and [3H]-raclopride binding in the SNR (factor loadings are 0.814 and 0.703 respectively), indicating that both phenomena are under control of a similar central process. The above data are discussed in relation to the structure dependent dopamine D2 receptor mechanisms in a rat response to novelty.

Animals↗

Borrelia burgdorferi sensu lato infection in passerine birds from the Mazurian Lake region (Northeastern Poland).

The aim of the present study was to evaluate a potential role of different passerine birds species in Mazurian Lake region (northeast Poland) in the spread of Borrelia burgdorferi sensu lato, the spirochaete that causes Lyme disease. A total number of 1254 birds (representing 42 species) were captured during the 3-year study period. Blood samples were collected from birds and analyzed with a nested polymerase chain reaction technique in order to detect fragments of the pathogen DNA. Positive results were obtained in 4.2% of all blood samples. Specifically, B. burgdorferi s.l. were detected in tree pipit (Anthus Erivialis; 21.1% of 19 birds), dunnock (Prunella modularis; 15.8% of 19 birds), chaffinch (Fringilla coelebs; 12.7% of 166 birds), song thrush (Turdus philometos; 9.3% of 54 birds), nuthatch (Sitta euopea; 7.7% of 26 birds), hawfinch (Coccothraustes coccothroustes; 6.7% of 15 birds), robin (Erithacus rebecula; 5.1% of 256 birds), blackbird (Turdus merula; 4.2% of 71 birds) and wren (Troglodytes troglodytes; 3.7% of 27 birds). Additionally, the incidence of the infection was analyzed in relation to the habitat in which the birds resided (mixed coniferous forest or alder swamp forest), months of the study (from April to October), age and sex, but the differences were not statistically significant.

Age Factors↗

Rat behavior in two models of anxiety and brain [3H]muscimol binding: pharmacological, correlation, and multifactor analysis.

The contribution of GABAergic mechanisms to rat emotional behavior in two animal models of anxiety (open field test of neophobia and aversively conditioned freezing reaction), was confirmed by pharmacological analysis, using anxiolytic (midazolam) and anxiogenic (picrotoxin) compounds. Both substances are known to modulate GABA(A) receptors' activity in a positive or negative manner, respectively. It seemed, therefore, worthwhile to check whether the behavioral parameters measured in these animal models of anxiety correlate with [3H]muscimol binding (a highly selective GABA(A) receptor ligand) in different brain structures of nai;ve rats, with a view to establish the role of genetically determined expression of local GABA(A) receptors in the organization of rat emotional and motor behavior. Correlation analysis revealed no links between individually determined expression of GABA(A) receptors (quantitative receptor autoradiography) in the brain structures, and the emotional behavior of nai;ve, drug-free animals, in both tests. Factor analysis confirmed that animal behavior in both tests was under control of different central processes. Moreover, none of the behavioral and ligand binding parameters loaded on the same factor, confirming the negative results of the correlation study. The present results indicate that the origin of emotions is a complex phenomenon, probably involving the interaction between GABA-ergic innervation of many brain structures.

Analysis of Variance↗

Neurotransmitter levels and [3H]muscimol binding sites in the brain of rats selectively bred for alcohol preference and non-preference.

Alcohol-naive high- (Warsaw High Preferring; WHP) and low- (Warsaw Low Preferring; WLP) preferring lines of rat were studied to determine the distribution and density of [3H]muscimol binding sites in the brain using quantitative autoradiography. The results have shown no difference in the density of [3H]muscimol binding sites in the cingulate and frontal cortex, dorsal and ventral striatum, lateral and medial septum, caudate-putamen, nucleus accumbens in the both lines of animals. In the separate experiments, the levels of neurotransimitters were measured in the frontal cortex, hippocampus and striatum of the WHP and WLP rats. The content of dopamine was significantly lower in the striatum of the WHP rats as compared to the WLP animals. The levels of serotonin and noradrenaline were without any important differences in the examined structures of both lines of rats.

Alcohol Drinking↗

Exploratory activity and a conditioned fear response: correlation with cortical and subcortical binding of the alpha4beta2 nicotinic receptor agonist [3H]-epibatidine.

Rat behavior in the open field and the conditioned fear response test was correlated with specific binding of the alpha4beta2 nicotinic acetylcholine receptor (nAChR) agonist, [3H]-pibatidine, assayed in different brain structures by autoradiography. A significant positive correlation was found between the ligand binding in the frontal cortex (r = 0.529, p < 0.011), the entorhinal cortex (r = 0.603, p < 0.003), and CA1 layer of the hippocampus (r = 0.465, p < 0.029), and the conditioned freezing reaction in the contextual fear conditioning test. In the frontal cortex, there was also a significant positive correlation between [3H]-epibatidine binding and preconditioned freezing reaction (r = 0.469, p < 0.028), and a negative correlation with rat motility (r = -0.452, p < 0.035). Rat motor activity correlated in a negative way with preconditioned freezing reaction (r = -0.436, p < 0.043), and in a positive way with the number of entries into the central sector of the open field (r = 0.690, p < 0.001). The neophobia-related parameter of the open field behavior (the number of central entries) did not correlate with the [3H]-epibatidine binding. Factor analysis confirmed these findings and showed that rat behavioral parameters measured in the tests of neophobia and conditioned freezing were loading on different factors, thus, pointing to separate central mechanisms operating in both behavioral models of anxiety. Furthermore, factor analysis showed that rat conditioned freezing behavior and [3H]-epibatidine binding in the CA1 layer of the hippocampus and enorhinal cortex, represented similar central processes. These findings suggest that rat emotional reactions evoked by different stressors (neophobia vs. conditioned fear) are differently regulated by the central cholinergic system. The presented data indicate also a significant, structure dependent correlation between rat conditioned emotional reaction and the alpha4beta2 nAChR ligand binding, in the rat cortical forebrain structures.

Animals↗

Lack of changes in cortical [3H]-muscimol binding in rats sensitized to nicotine-induced enhancement of dopamine metabolism.

It was proposed that chronic nicotine treatment may induce adaptive changes in GABAA receptors, thus leading to the attenuation of a GABAergic inhibition of dopaminergic neurons. This putative mechanism might underlie the sensitization to nicotine-induced increase in locomotor activity and dopamine metabolism; i.e. phenomena highly significant to the dependence-producing effects of this psychostimulant. To test this hypothesis, in the present study we have analyzed the influence of acute and repeated treatment of rats with nicotine on the binding of a highly selective and competitive GABAA receptor agonist, [3H]-muscimol. The binding was investigated by autoradiography in different brain cortical structures. It was found that nicotine given at the dose stimulating locomotor activity (0.6 mg/kg, sc), markedly increased striatal HVA concentration in the group of animals chronically pretreated (for 6 days) with this psychostimulant. Neither acute nor repeated nicotine administration changed in a significant way the [3H]-muscimol binding to brain cortical structures. Thus, the hypothesis about the role of adaptive changes in GABAA receptors in the enhancement of the biochemical and behavioral effects of nicotine was not confirmed.

Animals↗