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Biomedical subjects

Wojciech Kostowski

Publications and source records attributed to Wojciech Kostowski.

13 recordsLinked to original sources

The effects of central administration of physostigmine in two models of anxiety.

The effects of intracerebroventricular and intraseptal (the medial septum) administration of a prototypical acetylcholinesterase inhibitor (AChE-I), physostigmine, and a classic benzodiazepine midazolam on rat behavior in the open field test of neophobia and in the conditioned fear test (freezing reaction) were examined in rats. In the open field test of neophobia midazolam and physostigmine increased at a limited dose range, rat exploratory activity, after intracerebroventricular injection. Physostigmine produced in addition the hyperlocomotory effect. Following intraseptal injections, only physostigmine selectively prolonged the time spent by animals in the central sector of the open field. In the model of a conditioned fear, both midazolam and physostigmine inhibited rat freezing reaction to the aversively conditioned context after intracerebroventricular, but not after intraseptal, pretrial drug administration. The presented data support the notion about the selective anxiolytic-like effects of some AChE-Is. It appears, therefore, that the calming and sedative effects of AChE-Is observed in patients with Alzheimer's disease may be directly related to their anxiolytic action, independent of an improvement in cognitive functions, which in turn may decrease disorientation-induced distress and anxiety.

Animals↗

Chorda tympani nerve transection does not alter operant oral self-administration of ethanol in the rat.

In experimental conditions, it has been suggested that taste factors may contribute to ethanol preference in rodents. The aim of the current study was to assess the effects of transection of a gustatory branch of the seventh cranial nerve, the chorda tympani (CT), on operant self-administration of ethanol in rats. Male Wistar rats were trained to lever press for 8% [volume/volume (vol./vol.)] ethanol solution. When 8% ethanol intake stabilized, the CT nerve was transected bilaterally in six subjects. Another group received sham operations. There were no between-group differences in terms of self-administration of 8% ethanol, either before or after surgery. In addition, self-administration of 2% and 4% ethanol, measured after surgery, did not differ between the groups. In a control experiment, two-bottle consumption of as well as preference for 0.625% [weight/volume (wt./vol.)] sucrose were significantly decreased in the lesioned subjects. The results may indicate that gustatory input of the CT nerve is not necessary for maintenance of operant oral self-administration of ethanol.

Animals↗

[Unexpected properties of angiotensin mediated by the AT2 receptor: possible therapeutic implications].

The renin-angiotensin-aldosterone system plays an important role in the regulation of electrolyte balance, body fluid volume and blood pressure. As yet, angiotensin II has been ascribed actions mediated by first type of receptors (AT1) such as increased blood pressure, antinatriuretic effect, cell proliferation. Since several years studies have been conducted on the role of second type receptor (AT2) through which angiotensin manifests its effects opposing those resulting from stimulation of type 1 receptor. They include: release of bradykinin and nitric oxide, vasodilation, natriuretic and antiproliferative effects. Blockade of the function of this receptor causes excessive reaction induced by action exerted on AT1 receptor.

Angiotensin-Converting Enzyme Inhibitors↗

Taste function in methadone-maintained opioid-dependent men.

It has been shown repeatedly that opioid dependence is associated with increased consumption of refined sugars. It is possible that this association results from altered taste reactivity in opioid-dependent subjects. Thus, in the present study, we compared taste responses to sweet, bitter, sour and salty solutions in methadone-maintained opioid-dependent men and healthy control subjects. The two groups did not differ in terms of rated intensity or pleasantness of sucrose (1-30%), quinine (0.001-0.005%), citric acid (0.02-0.1%) and sodium chloride (0.18-0.9%) solutions. Proportions of 'sweet-likers', i.e. subjects rating a 30% sucrose (0.88 M) solution as the most pleasant, were also similar in both groups. In line with the previous findings, the methadone-maintained subjects reported adding more table sugar to caffeinated beverages. The results of the present study suggest that changes in taste reactivity may not be responsible for altered dietary choices in opioid addicts.

Adult↗

Effects of D(1) receptor agonist SKF 38393 on male rat sexual behavior and postcopulatory departure in the goal compartment-runway paradigm.

Male rats were tested in an apparatus in which the goal compartment of the runway was connected with the start compartment by a one-way door. In this apparatus, the male spontaneously left the goal compartment containing the estrous female after a mount bout (the cluster of one or more copulatory events) and a new run started. This effect (the postcopulatory departure) seems to be due to the competition between the incentive value of the stimulus female and the runway. The dopamine D(1) receptor agonist SKF 38393 at the doses of 1-5 mg/kg sc significantly prolonged the time spent by the male in the goal compartment, while both run latency and run duration remained unaffected. Further analysis showed that the prolongation of the time in goal compartment results from increased duration of copulatory behavior accompanied by increased number of copulatory events. Although SKF 38393 did not influence the latency of postcopulatory departures, incomplete departures occurred in five out of eight males. In the free access to female conditions, the SKF 38393 did not influence copulatory performance, except for a reduction in the number of intromissions at the dose of 1 mg/kg sc. On the other hand, a significant reduction of postejaculatory ultrasonic vocalization was observed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam.

The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED(50)=39.8 nmol) and allopregnanolone (ED(50)=11.0 nmol) produced similar and dose-dependent protection against picrotoxin-induced seizures. Picrotoxin given intraperitoneally at the ED(85) dose decreased significantly the concentration of serotonin (5-HT), dopamine (DA), homovanilic acid (HVA) and 3,4-dihydroxyindolacetic acid (DOPAC), in the mouse striatum and the frontal cortex, in the period of time immediately preceding the onset of seizures. A single injection of allopregnanolone more potently, in comparison to midazolam, antagonized the biochemical action of picrotoxin, abolishing its effects on DA, HVA and 5-HT concentration, in the mouse striatum and the frontal cortex. These results for the first time provide a direct argument for an involvement of central dopaminergic and serotonergic systems in the seizure development. The present data add also to the accumulating evidence suggesting a favorable pharmacological profile for some neurosteroids currently considered to have a future role in the management of epilepsy.

Amino Acids↗

Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems.

The influence of pentylenetetrazol (PTZ)-induced kindling of seizures on the rat emotional behavior, the brain monoamine turnover rate measured in vitro, and correlation between behavioral and biochemical parameters, were examined in rats. The repeated administration of PTZ (35 mg/kg, ip) evoked kindled seizures in rats (Stage 4 or 5 of clonic-tonic convulsions-maximum). PTZ kindling caused selective changes in the rat emotional behavior, present in some models of anxiety only (a decreased freezing time in the conditioned freezing test and a decreased spontaneous and aversively conditioned ultrasonic vocalization). Simultaneously, PTZ kindling decreased the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, decreased the DA (HVA/DA ratio) turnover rate in the striatum, and inhibited the serotonin (5-HT) metabolism (5-HIAA/5-HT ratio) in the hippocampus and the prefrontal cortex. Correlations between dopamine (DA) or 5-HT regional metabolic rates in brain structures and animal behavior were either abolished or reversed in PTZ-kindled animals. It is concluded that both DA and 5-HT systems contribute to the emotional effects of PTZ-induced kindling of seizures. The hypothesis is put forward that PTZ kindling-induced inhibition of the serotonergic innervation may lead to the compensatory increase in 5-HT(1A) receptors in the dentate gyrus of the hippocampus, thus evoking the anxiolytic-like changes in animal behavior.

Animals↗

Drug addiction as drive satisfaction ("antidrive") dysfunction.

Drug addiction is a complex brain disorder, characterized by the loss of control over drug seeking and drug taking behavior, and by the risk of relapse, even after a prolonged period of abstinence. This disorder may have its source in a disturbed balance of drive-related behaviors, which control appetitive reactions aimed at seeking contact with an addictive substance. The act of consumption becomes more and more attractive, and the behavior takes on compulsive character. We suppose that drug addiction may involve a change in the mechanism of satisfaction of drives and states of satiation as well. To understand how the motivational processes are changed with the development of dependence, one must consider the mechanism of drive satisfaction and satiation states that occur in relation to the consumatory reflex. When a given drive is satisfied a state of fulfillment occurs. This state may be a result of a so-called "antidrive" mechanism (Konorski 1967). While a drive activity is characterized by general activation and tension, the drive satisfaction state ("antidrive") is characterized by relaxation and relief. When a particular drive is satisfied, the operation of other drives become possible. Therefore, we postulate that dysfunction of drive satisfaction leads to the sustained activation related to the current drug-related drive, which blocks the operation of other drives. In effect, uncontrolled compulsive appetitive behavior is released, and the operation of other drives is restrained, thus forcing the organism to focus on drug-related drive. The reason for an "antidrive" dysfunction may be related to adaptive changes which develop during a contact with an addictive substance.

Drive↗

Sucrose self-administration predicts only initial phase of ethanol-reinforced behaviour in Wistar rats.

AIMS: To characterize the relationship between the sucrose- and ethanol-reinforced behaviour in Wistar rats. METHODS: Subjects (n = 31) were trained to lever press for 8% (v/v) ethanol in an operant procedure where increasing concentrations of ethanol were introduced in the presence of 8% (w/v) sucrose. The sucrose concentration was subsequently decreased from 8 to 0%. Subjects were allowed to stabilize their intake of 8% ethanol over the next 20 days. RESULTS: Self-administration of 8% sucrose (ml/kg) significantly correlated with ethanol consumption (g/kg) on days 1-5 of the 8% ethanol self-administration period. This relationship completely disappeared during the subsequent weeks of ethanol self-administration (days 6-20). CONCLUSIONS: The results of the present study, combined with our previous findings, may indicate that self-administration of sucrose predicts only the initial phase of ethanol-taking behaviour in Wistar rats.

Animals↗

Relationship between dopamine D2 receptor-associated responses and operant ethanol self-administration in the rat: a factor analysis.

AIMS: To characterize the relationship between dopamine D(2) receptor-associated responses and operant ethanol self-administration in Wistar rats. METHODS: Thirty-two rats were first tested for apomorphine-induced sniffing and raclopride-induced catalepsy. Subsequently, the same subjects were initiated to lever press for ethanol in the sucrose-fading procedure. The subjects were allowed to respond for 8% v/v ethanol for 20 days. A factor analysis was used to characterize the relationship between D(2)-associated responses and parameters of sucrose and ethanol self-administration. RESULTS: The analysis revealed three factors accounting for 88.3% of the total variability. The first factor comprised only parameters of ethanol-reinforced behaviour. Parameters of sucrose self-administration and cataleptic responses to raclopride loaded heavily on the second and third factors, respectively. None of the factors comprised apomorphine-induced stereotypy. CONCLUSIONS: It appears that there is no relationship between apomorphine-induced sniffing, raclopride-induced catalepsy and operant responding for ethanol in Wistar rats. Our results, combined with previous reports, suggest that D(2) receptors are not primarily involved in the regulation of ethanol reinforcement.

Animals↗

Effect of subchronic ethanol treatment on plasma and cerebrospinal fluid leptin levels in rats selectively bred for high and low alcohol preference.

The effect of 5-week voluntary ethanol (EtOH) intake on plasma and cerebrospinal fluid (CSF) leptin levels was determined in adult male Warsaw high EtOH preferring (WHP) and low preferring (WLP) rats. EtOH treatment led to a decrease in leptin CSF concentration in WHP rats when compared to EtOH-naive WHP and control Wistar rats. On the contrary, in EtOH-treated WLP rats, both plasma and CSF leptin levels were increased in comparison with EtOH-naive animals. It can be concluded that EtOH treatment led to different response expressed especially by CSF leptin levels in WHP and WLP animals and it may be related to their genetic predisposition.

Alcohol Drinking↗

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↗

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↗