Biomedical subjects

Wojciech Kostowski

Publications and source records attributed to Wojciech Kostowski.

31 records · Page 2Linked to original sources

PubMed2002

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↗

PubMed2002

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Ethanol-reinforced behaviour predicts acquisition but not extinction of cocaine self-administration in the rat.

AIMS: The aim of the present study was to evaluate the relationship between operant oral ethanol self-administration and intravenous (i.v.) cocaine self-administration in male Wistar rats. METHODS: Twenty-four rats were trained to lever press for 8% v/v ethanol in the sucrose-fading procedure. The subjects with the highest (high ethanol responders [HER], n = 7) and lowest (low ethanol responders [LER], n = 7) ethanol intakes were selected for further experiments. After a wash-out period, during which i.v. catheters were implanted, the HER and LER were trained to nose-poke for cocaine infusions (0.33 mg/kg/infusion, a FR1 schedule) for nine daily sessions. RESULTS: The HER emitted more 'active' nose-pokes and obtained more cocaine infusions during sessions 2-4. Drug-seeking behaviour in the absence of cocaine reinforcement was then assessed for three consecutive extinction sessions. No between-group differences were found in terms of extinction of cocaine seeking. Locomotor responses to a novel environment were also similar in both groups. CONCLUSIONS: The present results suggest that a propensity to self-administer ethanol predicts more rapid acquisition of cocaine self-administration behaviour but does not influence subsequent behaviour during extinction.

Animals↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

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↗

PubMedDate not supplied

Intravenous self-administration of morphine and cocaine: a comparative study.

The aim of the present study was to estimate differences between patterns of morphine and cocaine use in Sprague-Dawley rats. This was done by first developing a set of conditions under which both drugs would be consistently self-administered over time. Subsequently rats were studied in groups of three, with only one rat actively self-administering morphine or cocaine while others two receiving yoked injections of either the drug or saline. With the exception of the 0.056, 0.1, 0.3 and 1.0 mg/kg/inj. training-dose regimens, intravenous (i..v.)self-administration of morphine was acquired at the dose of 0.56 mg/kg/inj. and subsequently maintained by rats. In contrast to morphine self-administration, rats rapidly acquired cocaine self-administration behavior at either the 0.3 or 0.56 injection dose and showed typical inverted U-shaped dose-response curves with maximal responding occurring at the injection dose of 0.3 mg/kg. With the "yoked" pairs of subjects, the rate of responding of the animal actually self-administering the drug was significantly higher than that of a paired animal which passively received injection whenever the first animal self-administered the drug. Thus, both morphine and cocaine served as a positive reinforcer of self-administration behavior under the fixed ratio 5 schedule of reinforcement. However, the 0.56 mg/kg injection dose of morphine resulted in an acquisition curve that was markedly, temporally delayed relative to the injection dose of cocaine. Finally, cocaine maintained higher rates of responding for its delivery than morphine. These differences between self-administration patterns of morphine and cocaine may provide significant information about the nature of drug reinforcement and dependence.

Animals↗

PubMedDate not supplied

Neonatal 5-hydroxytryptamine depletion induces depressive-like behavior in adult rats.

The influence of neonatal serotonergic lesion on adult behavior in locomotor and depression models was studied in male Wistar rats. When 3-day-old rats were injected intracisternally with 5,7-dihydroxytryptamine (5,7-DHT), a marked depletion of brain 5-HT was observed when animals were killed 3 months after the treatment. Brain catecholamine content was generally not changed by neurotoxin treatment. The behavioral consequence of intracisternal 5,7-DHT administration to developing rats consisted in reduction of adult rats' activity in the forced swimming test. Both desipramine, and, to the lesser extent, fluoxetine, reversed 5,7-DHT-induced immobility of animals.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Preliminary phenotypic characterization of the Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) lines of rats selectively bred for high and low ethanol consumption.

The Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) lines were bred from Wistar foundation stock to obtain lines of rats that differ in their preference for ethanol (EtOH) solutions. The WHP line has met major criteria for an animal model of alcoholism. The WHP rats voluntarily drink excessive amounts of alcohol while the WLP rats consume negligible amounts of alcohol. These patterns of EtOH consumption are stable in time and independent of the manner of access to EtOH solutions. Notably, when exposed to the increasing EtOH concentrations both WHP and unselected Wistar rats gradually increased total EtOH intake. In contrast, WLP rats when exposed to the increasing concentrations of EtOH consumed almost negligible amounts of EtOH. Furthermore, the WHP rats show an increased responsiveness to the stimulatory effects of low dose of EtOH.

Alcoholism↗

PubMedDate not supplied

Age-dependent effects of 5,7-dihydroxytryptamine on serotonin transporter in different brain areas in the rat.

In the present study, we investigated the [(3)H]citalopram binding using a quantitative autoradiography following intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal and adult male Wistar rats. One group of animals was injected with 5,7-DHT at 3 days after birth while the second group received the neurotoxin at 3 months after birth. Control group was injected with saline. Afterwards, all rats were examined at 4(th) months after birth to determine the serotonin (5-HT) and catecholamines concentrations using the liquid chromatography with electrochemical detection HPLC system and distribution and density of [(3)H]citalopram binding sites in the brain using the quantitative autoradiography. A marked depletion of brain 5-HT was observed in rats lesioned either in postnatal or adult period of life. Rats lesioned in their adult period of life showed dramatic reduction of 5-HT transporter in all investigated brain areas (i.e.the frontal cortex, entorhinal cortex, hippocampus, caudate-putamen, nucleus accumbens and ventral tegmental area). On the other hand, administration of 5,7-DHT to newborn rats failed to reduce 5-HT transporter sites in the ventral tegmental area, and produced only slight or moderate reduction in the nucleus accumbens. Thus, it appears that the mesolimbic ventral tegmental area-nucleus accumbens systems are relatively more resistant to 5,7-DHT neurotoxicity in the early postnatal period.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Operant self-administration of ethanol in Warsaw high-preferring (WHP) and Warsaw low-preferring (WLP) lines of rats.

The results of the present experiment demonstrate that ethanol-preferring line of rats (WHP), and ethanol-nonpreferring line of rats (WLP) are able to acquire and maintain lever pressing reinforced by EtOH (oral operant EtOH self-administration) under FR-1 and FR-2 schedule of reinforcement. On the other hand, WHP rats but not WLP rats, displayed the high ability to acquire and maintain robust lever pressing for EtOH under FR-3 procedure. These data suggest that EtOH possesses stronger reinforcing properties in WHP rats. Nevertheless, WLP rats are able to acquire operant self-administration of EtOH when response demand of the reinforcement schedule is lower. Thus, both lines of rats can differ substantially in the amount of EtOH intake when its access is continuous and freely available, but less fundamentally when they respond for EtOH reward under low-demand schedules of partial reinforcement.

Alcohol Drinking↗