Biomedical subjects

W Kostowski

Publications and source records attributed to W Kostowski.

At least 181 records · Page 10Linked to original sources

PubMedDate not supplied

Alcohol drinking in rats treated with 5,7-dihydroxytryptamine: effect of 8-OH-DPAT and tropisetron (ICS 205-930).

5,7-Dihydroxytryptamine (5,7-DHT) was administered ICV to Wistar male rats. Lesioned rats displayed higher preference for ETOH than sham-lesioned animals. Among 5,7-DHT-pretreated rats 38% became high-preferring, while only 22% of sham-lesioned rats displayed this behavioural pattern (p < 0.05). Both 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; the agonist of serotonin 5-HT1A receptors) and tropisetron (ICS 205-930, the antagonist of 5-HT3 receptors) reduced ETOH consumption in high-preferring, sham-lesioned rats. However, in 5,7-DHT rats the effect of 8-OH-DPAT was completely abolished, while tropisetron retained its antipreference activity. Therefore, it seems that 5-HT1A autoreceptors are critically involved in 8-OH-DPAT action, while 5-HT3 receptor sites responsible for tropisetron action are located beyond the 5-HT system.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Evidence that the amygdala is involved in the inhibitory effects of 5-HT3 receptor antagonists on alcohol drinking in rats.

Two 5-HT3 receptor antagonists, tropisetron (1 and 10 ng) and ondansetron (10 and 100 ng) were tested for effects on ethanol drinking in Wistar male rats after bilateral microinjection into the amygdala. The animals had limited access (2 h/day) to the 10% (v/v) ethanol solution, food and water were available ad lib during the scheduled access period. Both drugs caused a decrease in ethanol drinking. Tropisetron (1 and 10 ng) decreased ethanol intake during the first hour of access. The lower dose (10 ng) of ondansetron was more effective than the higher (100 ng) dose. The finding implicates amygdaloid 5-HT3 receptors in the mechanism of ethanol intake in Wistar rats.

Alcohol Drinking↗

PubMedDate not supplied

5-HT3 receptor antagonist, tropisetron, does not influence ethanol-induced conditioned taste aversion and conditioned place aversion.

Numerous works have demonstrated an interaction between 5-HT3 receptor antagonists and some of the effects of ethanol (EtOH) using biochemical, electrophysiological, and behavioral techniques. Thus 5-HT3 antagonists are capable of reducing EtOH-induced release of dopamine in the nucleus accumbens, EtOH-induced hyperlocomotion, and voluntary EtOH consumption in laboratory animals. In addition to its rewarding effect, EtOH possesses aversive properties as demonstrated in the conditioned taste aversion (CTA) and conditioned place aversion (CPA) paradigms. The role of 5-HT3 receptors in aversive effects of EtOH remains, however, unknown. We decided to study the effect of 5-HT3 antagonist, tropisetron, on aversive properties of EtOH (1.5 g/kg i.p.) in rats using the CTA and CPA models. In addition, effect of tropisetron on morphine (Mf)-induced CTA (10.0 mg/kg SC) was investigated. Tropisetron (0.001-0.5 mg/kg) did not influence CTA produced by EtOH and Mf. When given alone, it failed to produce any taste conditioning. Furthermore, tropisetron did not modify CPA induced by EtOH. Our results suggest that 5-HT3 receptors are not involved in aversive effects of acute doses of EtOH.

Animals↗

PubMedDate not supplied

Discriminative stimulus effects of ethanol: lack of antagonism with N-methyl-D-aspartate and D-cycloserine.

Several drug discrimination studies reported that both competitive and uncompetitive NMDA receptor antagonists substituted for ethanol stimulus in rats. In the present study we examined if compounds that act as agonists at the NMDA receptor complex, D-cycloserine (a partial agonist at the glycine positive modulatory site) and N-methyl-D-aspartate (an agonist at the glutamate binding site), could antagonize the discriminative stimulus effects of ethanol. Rats were trained to discriminate between IP administered 1.0 g/kg of ethanol (10% v/v) and saline under a sweetened milk-reinforced fixed ratio 10 (FR10) schedule of reinforcement. When the animals met the discriminative criteria, antagonism tests were conducted with D-cycloserine (0.3-10.0 mg/kg, IP) and N-methyl-D-aspartate (15.0-60.0 mg/kg, IP). Neither D-cycloserine nor N-methyl-D-aspartate antagonized the ethanol-mediated discriminative stimulus effects. In addition, D-cycloserine (3.0-300.0 mg/kg, IP) did not substitute for ethanol. These results indicate that at least certain agonists at the NMDA receptor complex do not attenuate the ethanol interoceptive cue in the rat.

Alcohol Deterrents↗

PubMedDate not supplied

5,7-dihydroxytryptamine lesion does not affect ethanol-induced conditioned taste and place aversion in rats.

The effect of the lesion of central serotonergic neurons by 5,7-dihydroxytryptamine (5,7-DHT), on ethanol-induced taste and place aversion conditioning was studied in male Wistar rats. Control biochemical analysis revealed that 5,7-DHT (250 micrograms per rat, free base, i.c.v.) produced marked and selective depletion of serotonin (5-HT) in the hippocampal formation and the limbic forebrain complex. Ethanol-induced (1.5 g/kg, i.p.) conditioned taste aversion (CTA) to saccharin solution was unaffected by the lesion of central serotonergic neurons. The 5,7-DHT-lesioned and sham-lesioned rats showed comparable ethanol-induced CTA even 30 days after the last ethanol injection. Similarly, ethanol-induced (1.5 g/kg, i.p.) conditioned place aversion (CPA) was unaffected by 5,7-DHT administration. These results suggest that central serotonergic pathways are not primarily involved in the aversive effects of high ethanol doses in rats.

5,7-Dihydroxytryptamine↗

PubMedDate not supplied

Effects of N-methyl-D-aspartate receptor antagonists on reinforced and nonreinforced responding for ethanol in rats.

Results of several recent studies indicate that the discriminative stimulus effects of ethanol are related, at least partially, to ethanol-induced decrease in the N-Methyl-D-aspartate (NMDA) receptor function. The role of NMDA receptors in ethanol reinforcement remains still unclear. The aim of the present study was to evaluate the effects of two novel NMDA receptor antagonists in rats lever pressing for 8% ethanol in the oral self-administration procedure. In addition, the effects of the drugs on intensity of nonreinforced responding for ethanol (i.e., "experimental craving") were examined in the extinction procedure. To assess selectivity of the drugs' actions the same range of doses was tested in rats lever pressing for water (control experiments). A low-affinity, uncompetitive NMDA receptor antagonist, MRZ 2/579 (2.5-7.5 mg/kg) selectively and dose-dependently decreased ethanol self-administration. This compound exerted also selective effects on nonreinforced responding for ethanol with lower dose (2.5 mg/kg) increasing and higher dose (5 mg/kg) suppressing operant behavior in the extinction procedure. MRZ 2/579 (5 mg/kg) did not alter open field activity when given in combination with either saline or ethanol (0.5-1 g/kg). In contrast, a glycineB site antagonist, MRZ 2/576 (2.5-7.5 mg/kg) did not produce any selective effects on either reinforced or nonreinforced lever pressing for ethanol. The present results suggest that MRZ 2/579 may selectively suppress both ethanol self-administration and experimental ethanol craving.

Animals↗

PubMedDate not supplied

Glutamate concentration in whole saliva and taste responses to monosodium glutamate in humans.

It is universally accepted that saliva plays an important role in taste sensations. However, interactions between constituents of whole saliva and the five basic taste modalities are still poorly understood. The aim of the present study was to evaluate possible relationship between endogenous glutamate (Glu) levels in whole saliva and taste responses to a prototypic umami substance, monosodium glutamate (MSG; 0.03-10.0%). Rated intensity and pleasantness of MSG taste was studied in healthy volunteers divided into a high glutamate (HG) in saliva (HG; n = 19) and low glutamate in saliva (LG; n = 18) group based on the median split level of salivary Glu. The HG and LG group did not differ in terms of electrogustometric thresholds, rated intensity of the MSG samples and pleasantness of distilled water and the lower MSG concentrations (0.03-1.0%). Perceived intensity of water taste was significantly (P < 0.05) higher in the LG subjects. The LG group rated the higher MSG concentrations (3.0-10.0%) as more unpleasant (P < 0.01). The difference remained significant after controlling for a between-group difference in age. The present results suggest that individual differences in salivary Glu levels may alter hedonic responses to suprathreshold MSG concentrations.

Adult↗

PubMedDate not supplied

Involvement of nicotinic acetylcholine receptors in the regulation of alcohol drinking in Wistar rats.

The aim of the present study was to determine if nicotinic acetylcholine receptors (nAChRs) might be involved in the regulation of alcohol intake by Wistar rats. A non-selective nAChR agonist, nicotine, and a non-competitive nAChR antagonist, mecamylamine, were tested in alcohol-preferring Wistar rats maintained on a limited access (4 h/24 h) to ethanol (10%, v/v). In addition, the effects of nicotine and mecamylamine on intake of standard laboratory chow were studied in a separate control experiment. Nicotine (0.1-0.6 mg/kg, s.c.) decreased ethanol consumption, but had no effect on food intake. In contrast, mecamylamine (1-3 mg/kg, s.c.) did not alter ethanol drinking even at the dose (3 mg/kg) which significantly decreased food intake. These results suggest that activation of nAChRs may selectively reduce ethanol consumption in outbred Wistar rats.

Alcohol Drinking↗

PubMedDate not supplied

Development of alcohol deprivation effect in rats: lack of correlation with saccharin drinking and locomotor activity.

The present study addressed the relationship between the parameters of saccharin drinking behaviour and locomotor activity in an open field environment and long-term alcohol self-administration. In a 22-day initiation phase, male Wistar rats were presented with increasing concentrations of ethanol (2-8%, v/v) in a choice with water. The rats were then given the choice between water and two ethanol solutions (8 and 16%). Every 28 days, ethanol was withdrawn for 5 days. The ethanol intake and the transient increase in ethanol consumption after each of six deprivation episodes (alcohol deprivation effect) was monitored and correlated with parameters of the subsequent saccharin drinking and open field tests. The total ethanol intake (g/kg/24 h) as well as the consumption of 16% ethanol were stable over time. However, the magnitude of the alcohol deprivation effect increased with the repeated deprivation episodes. None of the parameters measured in the open field or the saccharin drinking tests correlated with either ethanol consumption or the alcohol deprivation effect. These results suggest that (1) repeated episodes of ethanol deprivation may increase the magnitude of the alcohol deprivation effect, (2) neither saccharin drinking nor locomotor activity correlates with long-term ethanol drinking behaviour in rats.

Animals↗

PubMedDate not supplied

Operant responding for ethanol in rats with a long-term history of free-choice ethanol drinking.

Wistar rats were allowed to drink ethanol in a two-bottle (water vs 2-8% v/v ethanol) and then in a three-bottle choice paradigm (water vs 8% ethanol vs 16% ethanol, v/v). After 7 months of free access to alcohol, the subjects were trained to respond for 8% ethanol in an operant procedure. No relationship was found between prior alcohol drinking and lever pressing for ethanol.

Alcohol Drinking↗

PubMedDate not supplied

Taste responses in sons of male alcoholics.

The aim of the present study was to compare taste responses (intensity and pleasantness/unpleasantness) to sweet, bitter, sour, and salty solutions in sons of male alcoholics (SOMAs) and control subjects with no family history of alcoholism. In addition, responses to Coca-Cola flavour were evaluated in both groups. Unpleasantness of salty solutions was significantly enhanced and intensity of sour solutions tended to be higher in the SOMAs. There were no other differences between the groups. Thus, contrary to previous suggestions, genetically determined vulnerability to alcohol dependence may not be associated with altered responses to sweet substances. The present findings would rather suggest that increased aversive responses to salt taste may predict future development of alcohol dependence.

Adolescent↗

PubMedDate not supplied

Changes in ethanol preference by rats treated with gamma1 and gamma2 GABA(A) receptor subunit antisense oligodeoxynucleotides.

Micro-injections (10 nmol/day over 5 days) of antisense oligodeoxynucleotides (aODNs) to gamma-aminobutyric acid A (GABA(A)) receptor alpha1 and gamma2 subunits reduce the mRNA for these subunits in rat brain. In this study, the effects of alpha1 and gamma2 subunit aODNs on rat alcohol preference were investigated. Reduction of the alpha1 subunit mRNA decreased, whereas reduction of the gamma2 subunit mRNA increased, ethanol intake in rats.

Analysis of Variance↗

PubMedDate not supplied

Taste responses in alcohol-dependent men.

The aim of the present study was to compare taste responses to sweet, bitter, sour and salty solutions in male alcoholics and control subjects. The 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. The proportion of sweet-likers was also similar in both groups.

Adult↗

PubMedDate not supplied

Novelty-seeking behaviour and operant oral ethanol self-administration in Wistar rats.

The aim of the present study was to investigate the relationship between novelty-seeking behaviour and operant oral ethanol self-administration in Wistar rats. The open field and novel object test was used to assess novelty-seeking. Ethanol self-administration was initiated in an operant procedure where ethanol was introduced in the presence of sucrose. Eighteen out of 32 rats were successfully initiated to lever-press for 8% (v/v) ethanol. None of the parameters assessed in the open field (horizontal activity, rearings) or novel object test (number of contacts with an object, exploration time) differed between the initiated and non-initiated subjects. In addition, correlational analysis revealed that response to novelty did not predict individual differences in ethanol intake in the initiated rats. These results suggest that there is no relationship between novelty-seeking and operant ethanol self-administration in Wistar rats.

Administration, Oral↗

PubMedDate not supplied

Lack of ifenprodil anxiolytic activity after its multiple treatment in chronically ethanol-treated rats.

AIMS: The purpose of this study was to assess the anxiolytic activity of ifenprodil in Warsaw high-preferring (WHP) and low-preferring (WLP) rats after chronic ethanol treatment. METHODS: WHP and WLP animals, their paired-ethanol-naive groups and control Wistar rats were treated with ifenprodil (1.0 mg/kg, intraperitoneally) for 21 consecutive days. Anxiolytic activity was evaluated by using the two-compartment exploratory test. In addition, the locomotor activity paradigm was also assessed. RESULTS: Ifenprodil did not affect this paradigm in all investigated groups. The ethanol treatment led to lowering of anxiolytic scores in WHP rats. Multiple ifenprodil administration showed an anxiogenic-like activity in both WHP- and WLP-ethanol-treated groups. CONCLUSIONS: Our results suggest that, under some conditions, the role of ifenprodil in the treatment of alcoholism may be insufficient to support its use.

Alcohol Drinking↗

PubMedDate not supplied

Effects of 5-HT3 receptor agonists on voluntary ethanol intake in rats maintained on a limited access procedure.

Recent evidence from a variety of laboratory studies suggests that the central effects of ethanol (EtOH) are mediated by serotonin 5-HT3 receptors. Notably, EtOH is able to potentiate 5-HT action on 5-HT3 ionophore, and 5-HT3 antagonists are known to reduce certain effects of EtOH. In the present study, we evaluated the effects of two agonists of 5-HT3 receptors, 2-methyl-5-HT (2-Me-5-HT) and m-chlorophenylbiguanide (m-CPBG) that were microinjected i.c.v. and into the nucleus accumbens (NAC) on EtOH intake in Wistar rats with high EtOH preference. 2-Me-5-HT given i.c.v. (1 and 10 microg per rat) and into the NAC (bilaterally 1 and 10 microg per site) significantly reduced EtOH intake in the limited access paradigm (2h session). On the other hand m-CPBG was inactive after intra-NAC administration. It is concluded that central 5-HT3 receptors are involved in the regulation of EtOH consumption.

Alcohol Drinking↗

PubMedDate not supplied

Prior exposure to MK-801 sensitizes rats to ethanol-induced conditioned taste aversion.

Pretreatment with an uncompetitive NMDA receptor antagonist, dizocilpine [(+)MK-801; six daily injections of 0.1 or 0.2 mg/kg, i.p.] significantly enhanced subsequent 1.5 g/kg ethanol-induced conditioned taste aversion (CTA). In a control experiment, dizocilpine (0.05-.2 mg/kg) produced only a marginal CTA. Thus, pre-exposure to low, non-aversive doses of MK-801 may sensitize rats to the aversive stimulus effects of ethanol.

Animals↗

PubMedDate not supplied

Saccharin drinking rather than open field behaviour predicts initial ethanol acceptance in Wistar rats.

This study examined the relationship between saccharin drinking, open field behaviour and ethanol drinking in Wistar rats. Correlational analysis revealed that both absolute saccharin drinking and an increase in total fluid intake in the presence of saccharin positively correlated with the initial acceptance of increasing ethanol concentrations in a two-bottle choice situation (2-8% v/v ethanol vs water). This relationship disappeared, however, during further weeks of ethanol drinking when ethanol was available in a three-bottle choice situation (8% ethanol vs 16% ethanol vs water). In contrast, none of the behavioural parameters measured in the open field test (forward locomotion, rearings, central entries, time in central area) correlated with subsequent ethanol consumption. These results indicate that saccharin drinking, rather than open field parameters, may predict subsequent ethanol intake during the initial period of exposure to low ethanol concentrations.

Alcohol Drinking↗