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Biomedical subjects

W Kostowski

Publications and source records attributed to W Kostowski.

265 records · Page 15Linked to original sources
PubMedDate not supplied

Limbic mechanisms of anxiolytics acting on 5-HT receptors.

The role of brain serotonergic system innervating hippocampus and nucleus accumbens in the anxiolytic-like action of the 5-HT1A receptor agonists and 5-HT3 receptor antagonists, is discussed. The data on the effects of intrastructural microinjections of selective serotonergic agonists and antagonists in the Vogel and open field (neophobic reaction) tests are described and critically reviewed. It is concluded that both postsynaptic inhibition of the temporal lobe function (the hippocampus), and attenuation of the cell body firing of the raphe neurons appears to be important elements of anti-anxiety action of benzodiazepines and 5-HT1A receptor antagonists. Thus, it is hypothesized that this dual mechanism of the 5-HT1A receptor agonists and the 5-HT3 receptor antagonists action cooperates synergistically in the processing of emotional functions.

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

[A new concept of antidepressant drugs action: clinical and preclinical data].

The authors propose a new concept of antidepressant drug action based on adaptive receptor changes occurring in the course of chronic antidepressant treatment. Some clinical data and more equivocally preclinical studies indicate an enhancement of activity of those neurotransmitter systems which exert an activating impact on diverse cns functions (dopaminergic and alpha-1 adrenergic receptors). On the other hand the same treatment is found to inhibit the activity of central inhibitory systems (e.g. serotonergic and GABAergic receptors), thus resulting in an increase of positive reinforcement and psychomotor processes in the cns.

Antidepressive Agents↗
PubMedDate not supplied

Studies on the effects of certain 5-HT-3 receptor antagonists on ethanol preference and withdrawal seizures in the rat.

We tested how certain antagonists of 5-HT-3 receptors affect ethanol consumption and withdrawal seizures in ethanol-dependent Wistar male rats. Low doses of tropisetron (0.001-0.01 mg/kg ip) and ondansetron (0.00025 mg/kg ip) reduced ethanol consumption and preference. Increased ethanol intake was observed, however, after administration of higher doses of ondansetron (0.125 g/kg ip) and granisetron (0.125-0.25 mg/kg ip). Audiogenic seizures in rats withdrawn from ethanol were attenuated by low doses of tropisetron and ondansetron.

Acoustic Stimulation↗
PubMedDate not supplied

The effect of drugs interacting with serotonergic 5HT3 and 5HT4 receptors on morphine place conditioning.

The effect of 5HT3 and 5HT4 active compounds on the motivational properties of morphine has been examined in the place conditioning (PC) paradigm using unbiased procedure. Place conditioning with morphine produced significant place preference. Pretreatment with the DAU 6285 (mixed 5HT3 antagonist--5HT4 antagonist) abolished morphine-induced PC. Ondansetron (selective 5HT3 antagonist) attenuated morphine place preference at the dose of 0.1 mg/kg. BIMU 8 (mixed 5HT3 antagonist--5HT4 agonist) failed to modify morphine PC in the 0.001-0.1 mg/kg dose range. While ondansetron given alone failed to produce place conditioning, pairing of BIMU 8 (0.001 mg/kg) induced significant place preference. On the other hand, animals were frequently avoiding compartment paired with the injection of DAU 6285. These findings suggest that 5-hydroxytryptamine by means of 5HT4 receptors mediates appetitive properties of morphine induced-stimuli and suggest that 5HT4 receptor may be involved in the brain reward and reinforcement processes.

Animals↗
PubMedDate not supplied

Comparative study of nifedipine and isradipine in animal models of ethanol dependence.

The effects of calcium channel inhibitors on ethanol intake and dependence in Wistar rats were studied. Nifedipine and isradipine were suspended in 1% Tween 40 saline solution and administered ip 60 min prior to testing. Audiogenic seizure response evaluation was performed after 5 days of ethanol treatment. Both nifedipine and isradipine significantly reduced the intensity score of convulsions and, in doses of 2.5 and 5.0 mg/kg, respectively, abolished them. Both drugs significantly reduced ethanol preference and intake in the high preference group of animals. Our results support the observations that certain dihydropyridine derivatives are capable of attenuating both ethanol preference and physical dependence.

Alcohol Drinking↗
PubMedDate not supplied

Selective breeding of rats differing in voluntary ethanol consumption.

Selective breeding of Wistar rats for the voluntary ethanol consumption is being carried out. Five generations have been achieved of ethanol high preferring and ethanol low preferring lines. Significant segregation between lines has been accomplished. In general, the results obtained replicate the previous findings with the genetic selection for voluntary ethanol consumption with the exception of poor results of downward selection.

Alcohol Drinking↗
PubMedDate not supplied

Open field behavior of rats reared in different social conditions: the effects of stress and imipramine.

Behavioral changes in rats divided on the weaning day into two groups (crowded and isolated) were studied in the computerized open field. At the end of the experiment the effects of an acute stress (1 h long immobilization) on open field behavior, body weight and body temperature, were examined. In a separate experiment both groups of rats were chronically pretreated with tricyclic antidepressant imipramine (5.0 mg/kg, po), and subsequently exposed to the same stress procedure. Social deprivation significantly enhanced spontaneous locomotion and exploratory activity. Restraint stress significantly decreased exploration, body weight and temperature, in the isolated animals only. Chronic pretreatment of rats with imipramine significantly attenuated the effect of stress on motor and exploratory behavior, as well as stress-induced changes in body weight and temperature, in the group of isolated animals. The present data indicate sensitization to stress of behavioral and vegetative processes in socially deprived animals. The relationship between rearing conditions and behavioral and vegetative reactivity to the environmental challenges is confirmed.

Acute Disease↗
PubMedDate not supplied

Effects of 5-HT3 receptor antagonists on ethanol-induced hyperlocomotion in mice.

We tested how 5-HT3 receptor antagonists, tropisetron (TR) and ondansetron (ON) affect the hyperlocomotion induced by single dose of ethanol EtOH) in mice. EtOH in a dose-dependent manner (0.5-2.0 g/kg ip) increased locomotion of mice. The effect of 2.0 g/kg of EtOH was reduced by ON (0.1 mg/kg and 1.0 mg/kg sc) and, to the lesser extent and only in limited dose range (0.01 mg/kg) by TR. Tropisetron (but not ON) increased concentrations of EtOH in the blood. The data suggest that 5-HT3 receptor is involved in EtOH-induced hyperlocomotion.

Animals↗
PubMedDate not supplied

Conditioned place preference after prolonged pre-exposure to ethanol.

Conditioned place preference (CPP) paradigm has been used to test ethanol (EtOH) rewarding properties after repeated (20 days) injections of EtOH. Rats injected with 0.5 g/kg ip of EtOH during pre-exposure period and CPP procedure showed significant place preference to the compartment paired with the drug. Animals receiving higher dose of EtOH (1.0 g/kg) showed no CPP but rather relative aversion to the paired compartment (relatively to saline-treated group). Our result suggests a development of sensitization to EtOH rewarding effect after prolonged administration of low dose of EtOH.

Animals↗
PubMedDate not supplied

Antagonism of behavioral effects of electroconvulsive shock but not those of desipramine by the selective 5-HT-3 receptor antagonist, ondansetron.

The influence of ondansetron (ON) on desipramine (DMI) and electroconvulsive shock (ECS) effects in the open field (OFT) and forced swim test (FST) were studied in Wistar male rats. ON failed to influence the action of DMI but abolished stimulatory effect of ECS in the OFT and, in the lower dose (0.01 mg/kg) reduced ECS action in the FST. This result suggests that 5-HT-3 receptors are involved in behavioral effects of ECS but not DMI.

Animals↗
PubMedDate not supplied

Recent advances in the GABA-A-benzodiazepine receptor pharmacology.

Gamma-aminobutyric acid (GABA) acts on pharmacologically and functionally distinct receptors. These sites designated GABA-A and GABA-B receptors, differ with regard to their ionic characteristic and pharmacological properties. The most important distinction is, that the GABA-A receptor is associated with chloride channel and with membrane recognition sites for benzodiazepines. During the past decade numerous studies have made it possible to obtain more detailed knowledge of the structure and properties of the GABA-benzodiazepine receptor complex, which is made up of at least two distinct sites designated as BZD-1 and BZD-2 receptors. Third type, designated as peripheral type is located in the mitochondrial membrane and may regulate a steroidogenesis in the CNS. Molecular cloning studies showed a heterogeneity of GABA-A receptors, which are composed of multiple subunits (alpha, beta, gamma, delta and ro), which form distinct isoreceptors. New classes of GABA-BZD agonists such as zolpidem act selectively upon certain isoreceptors thus showing characteristic pharmacological properties. Recent studies provided detailed information on the interaction of ethyl alcohol (Et-OH) with GABA-BZD receptor complex. The most important finding is, that there are Et-OH sensitive and Et-OH resistant GABA-A receptor isoforms. Recent evidence reinforces the possibility, that reduced activity of the brain GABA-ergic system is associated with mechanism of depression.

Animals↗
PubMedDate not supplied

5-HT3 receptors and central effects of ethanol.

This review discusses recent experimental findings in serotonin-3 (5-HT3) receptors and ethanol (EtOH) research. The role of these receptors in central effects of EtOH including the effects of 5-HT3 agonists and antagonists on EtOH intake, rewarding and aversive properties of EtOH and EtOH interoceptive cue is reviewed. It is now recognized that 5-HT3 receptors while involved in EtOH intake, EtOH tolerance and withdrawal and rewarding mechanisms do not play an important role in aversive effects of EtOH and EtOH discriminative stimulus. 5-HT3 receptors involved in EtOH consumption are supposedly located on dopaminergic neurons in the nucleus accumbens.

Alcoholism↗