Biomedical subjects

Z Amit

Publications and source records attributed to Z Amit.

At least 19 recordsLinked to original sources

PubMed2001

Caffeine, nicotine and mecamylamine share stimulus properties in the preexposure conditioned taste aversion procedure.

RATIONALE: The present study examined whether nicotine and caffeine, two of the most widely used psychoactive drugs, share stimulus properties in the preexposure conditioned taste aversion (CTA) procedure. OBJECTIVES: To determine whether nicotine would attenuate the formation of a caffeine-induced CTA and further assess whether pretreatment with mecamylamine, a nicotinic receptor antagonist, would reverse nicotine's attenuating effect of a caffeine-induced CTA. METHODS: Male Wistar rats were preexposed with one of three doses of nicotine (0.6, 1.2 and 2.0 mg/kg, s.c.) for three consecutive days, then 24 h following the final preexposure injection were conditioned with caffeine (20 mg/kg and 30 mg/kg, i.p.) in a standard two-bottle test. There were four conditioning trials and four drug-free test days. In a follow-up study, rats were pretreated with mecamylamine (2 mg/kg, i.p.) prior to preexposure injections with nicotine (0.6 mg/kg, i.p.), then subsequently conditioned with caffeine (20 mg/kg, i.p.) as described above. RESULTS: The lowest nicotine dose (0.6 mg/kg) attenuated the caffeine induced CTAs (20 mg/kg and 30 mg/kg) but the higher nicotine doses showed no such attenuating effect. In addition, mecamylamine reversed the nicotine-induced attenuation of the caffeine-induced CTA and also directly attenuated it. CONCLUSIONS: These results suggested that caffeine, nicotine and mecamylamine share overlapping stimulus properties and that the nature of this relationship may involve action at the nicotinic-cholinergic receptor.

Animals↗

PubMed2001

Effects of naltrexone on the intake of ethanol and flavored solutions in rats.

It has been suggested that the endogenous opioid system may mediate the intake of preferred fluids, perhaps through an attenuation of reinforcement properties causing a subsequent shift in palatability. The purpose of the present study was to investigate the effects of the nonspecific opiate antagonist naltrexone on the intake of 10% ethanol, 0.1% saccharin, 0.0006% quinine, 0.4% saccharin + 10% ethanol, and 0.4% saccharin + 0.04% quinine solutions. Fluid intake was measured in male Long-Evans and Wistar rats under 24-h continuous and 30-min limited-fluid-access drinking paradigms. All rats received injections of naltrexone hydrochloride (10 mg/kg, i.p.) for 5 days after baseline intake measures and were monitored for a further 5 days (after-treatment phase). Results indicated that naltrexone did not affect intake of any solution when fluids were available over 24 h. However, under limited-access conditions, naltrexone caused a decrease in the intake of all fluids except quinine in both rat strains. On the basis of these findings, it is possible that the effects of this dose of naltrexone were not due to any true conditioning effect on the reinforcement properties of ethanol, but perhaps to some nonspecific effect of the drug, such as an alteration in palatability or an attenuation of locomotor activity. As well, due to the inconsistent results in fluid intake across drinking paradigms, the present findings do not provide evidence for an effective role for opiate mediation in ethanol intake as well as any ethanol-sweet fluid intake interactions.

Alcohol Drinking↗

PubMed2001

Caffeine promotes an ethanol-induced conditioned taste aversion: a dose-dependent interaction.

The present study examined whether caffeine administered within a dose range previously shown to promote ethanol drinking would also alter an ethanol-induced conditioned taste aversion (CTA). The results revealed a dose-dependent interaction between caffeine and ethanol where caffeine (2.5 and 10 mg/kg) promoted an ethanol-induced CTA at a low ethanol dose (1.0 g/kg) but had no effect in blocking CTA at the higher ethanol dose (1.5 g/kg). These results were found to be unrelated to an alteration in ethanol metabolism, as caffeine had no effect in altering blood ethanol levels at the doses tested. In agreement with the reward comparison hypothesis, the present results suggest that rather than attenuate ethanol's "aversive" effects, caffeine may have promoted an ethanol-induced CTA by increasing the reinforcing efficacy of ethanol.

Animals↗

PubMed2001

Differences in locomotor response to an inescapable novel environment predict sensitivity to aversive effects of amphetamine.

Differences in locomotor response to an inescapable novel environment have previously been shown to predict sensitivity to amphetamine reward, where high responders (HR), compared to low responders (LR), showed greater initial sensitivity to amphetamine self-administration. The present experiments sought to extend these findings and assessed the relationship between locomotor response to an inescapable novel environment and conditioned taste aversion (CTA) with amphetamine and lithium chloride (LiCl). Male Sprague-Dawley rats were tested for their locomotor response to an inescapable novel environment and divided into high (HR) or low (LR) responders, based on whether their locomotor scores were above or below the median activity level of the subject sample. After several days, the animals were tested in a CTA procedure and conditioned with either amphetamine or lithium chloride. Compared to HR rats, LR rats showed greater sensitivity to amphetamine CTA at the doses tested. In contrast, the results with LiCl showed no relationship between locomotor response to an inescapable novel environment and CTA. Taken together, the present results suggest that LR, compared to HR, rats show less sensitivity to the rewarding effects of amphetamine because they are more sensitive to aversive effects of amphetamine, as reflected in CTA. In contrast, HR rats display less sensitivity to aversive effects of amphetamine, which may explain their greater propensity to self-administer amphetamine.

Animals↗

PubMed2001

Heterogeneity of Pneumocystis sterol profiles of samples from different sites in the same pair of lungs suggests coinfection by distinct organism populations.

Sterol profiles of samples taken from different sites of a Pneumocystis-infected human lung showed large variations in pneumocysterol similar to those that occur among samples from different patients. Thus, the influence of diet or drugs on pneumocysterol accumulation was ruled out, suggesting distinct phenotypic populations as the basis for the heterogeneity.

AIDS-Related Opportunistic Infections↗

PubMed2000

Preexposure effects of nicotine and acetaldehyde on conditioned taste aversion induced by both drugs.

Previous assessments have demonstrated an interaction between ethanol and nicotine in the conditioned taste-aversion (CTA) paradigm. The present study assessed whether acetaldehyde, the primary reinforcing metabolite of ethanol, would interact with nicotine as well. In six experiments, water-deprived male Wistar rats were preexposed to either acetaldehyde (0.2 or 0.3 g/kg, IP) or nicotine (0.8, 1.2, or 2 mg/kg, SC) for 3 consecutive days and then subsequently conditioned, 24 h later, with either nicotine (0.8, 1.2, or 2 mg/kg, SC) or acetaldehyde (0.2 or 0.3 g/kg, IP), respectively. There were 4 conditioning days and 4 drug-free test days, each spaced 72 h apart. On test days, animals were offered a free choice between water and saccharin. The results of the following set of experiments demonstrated a dose-related interaction between nicotine and acetaldehyde, where lower doses of each drug failed to attenuate CTA induced by one another, but a higher nicotine dose (2 mg/kg) attenuated the formation of a CTA induced by acetaldehyde (0.3 g/kg). It was argued that the primary metabolite of ethanol may play a role in the interaction between nicotine and ethanol previously observed.

Acetaldehyde↗

PubMed2000

Differences in the consumption of ethanol and flavored solutions in three strains of rats.

Several studies have shown a correlation between ethanol consumption and the intake of flavored solutions in rats, particularly sweet solutions. This observation, however, has not been shown in all strains of rats. The present study examined whether the intake of ethanol and that of flavored solutions would be related in Lewis (LEW), Wistar (WIS), and Wistar Kyoto (WKY) rats. During phase I, all rats were presented with water and a flavored solution following a continuous access paradigm as developed by Overstreet et al.: quinine (0.25% wt/vol), saccharin (0.1% wt/vol), ethanol (ETOH) (10% vol/vol), and saccharin-quinine (SQ) solutions (0.4% wt/vol-0.04% wt/vol). During phase II, fluid presentations were reduced to a 10-min limited access schedule and were presented in the same order. Results showed strain differences in intake and preference for ETOH and SQ during both phases, but not in quinine or saccharin intake. ETOH and saccharin intake were only correlated in the LEW strain during limited access drinking, while ETOH and SQ intake were correlated in the LEW strain as well as when all strains were collapsed during continuous drinking. These findings suggested that any association between ETOH and sweet intake may not be generalizable to all rat strains. The animals used in this study may have differed in taste sensitivity, as low ETOH-consuming LEW rats were sensitive to the bitter taste of quinine alone, as well as when mixed with saccharin. Sensitivity to bitter tastes may be an important predictor of low ETOH consumption and/or preference. These data provide further evidence for the role of taste factors in the mediation of voluntary ETOH consumption in rats.

Alcohol Drinking↗

PubMed2000

The effects of aminotriazole and acetaldehyde on an ethanol drug discrimination with a conditioned taste aversion procedure.

The present study was designed to investigate whether acetaldehyde shares stimulus properties with ethanol using the conditioned taste aversion (CTA) baseline of drug discrimination learning. Animals were trained to discriminate ethanol (0.8 g/kg, i.p.) from saline using 11 consecutive cycles consisting of a pairing day and three nonpairing days. On pairing days, all animals were injected with ethanol 30 min prior to a 20-min limited access to a saccharin solution (0.1% w/v) and then immediately injected with either LiCl (0.15 M, 1.8 meq) or distilled water. On the three following nonpairing days, animals were injected with saline and 30 min later presented with the same saccharin solution for 20 min. No injections followed on these nonpairing days. Results showed that animals acquired discriminative stimulus control for ethanol after seven pairings. Pretreatment with the catalase inhibitor did not alter the discriminative control for ethanol. Generalization tests revealed that acetaldehyde substituted for ethanol at a dose of 0.3 g/kg. The results of the present study suggest that catalase inhibition did not reverse or alter the discriminative stimulus effects of ethanol. However, generalization tests showed that acetaldehyde (0.3 g/kg) will substitute for ethanol suggesting that these two drugs share some similar properties.

Acetaldehyde↗

PubMed2000

Caffeine promotes ethanol drinking in rats. Examination using a limited-access free choice paradigm.

There is growing evidence that caffeine may alter the pattern of intake of a variety of drugs. The present study was designed to assess the effect of caffeine pretreatment on voluntary ethanol consumption. The first experiment examined the effect of caffeine on the acquisition of ethanol intake in a limited-access-choice procedure in which water and ethanol were presented concurrently. Male Wistar rats, exposed to food and water ad lib, were presented with a daily 1-h choice session between water and progressively increasing concentrations of ethanol (2-10%). Each ethanol concentration was made available for 4-6 days for a total of 20 days of access to ethanol. Intraperitoneal injections of caffeine (5 or 10 mg/kg) or saline were administered to the rats 30 min prior to each choice session. Caffeine produced a dose-related facilitation in ethanol drinking whereby the lower caffeine dose produced enhancement in ethanol drinking. The second experiment examined the effect of caffeine on the maintenance of established ethanol consumption. Male Wistar rats, initially acclimatized to increasing concentrations of ethanol (2%-10), were presented with an additional 18 ethanol (10%) presentations, comprised of a 6-day baseline period followed by 6 days of treatment where animals were given one of three doses of caffeine (2.5, 5 or 10 mg/kg) or saline prior to ethanol presentation. A final 6-day post-treatment period followed treatment. These results revealed an inverted-U effect of caffeine dose on ethanol ingestion where the low and high caffeine doses produced no effect but the moderate dose of 5 mg/kg enhanced ethanol drinking that persisted throughout the post-treatment period. A third experiment revealed that caffeine did not alter levels of blood ethanol within the time period used for the ethanol drinking session.

Alcohol Drinking↗

PubMed2000

Augmentation of corticosterone release by means of a caffeine-ethanol interaction in rats.

We examined whether the acute treatment with caffeine delivered before an ethanol injection would augment plasma corticosterone (CORT) levels. The effect of caffeine on blood ethanol levels was also assessed. After 10 days of acclimatization to the colony room conditions, male Wistar rats were injected with either caffeine (5 mg/kg, ip) or saline 30 min before the delivery of ethanol (0.8 g/kg, ip) or saline, respectively. Trunk blood was then collected at 15 and 30 min after the ethanol injection for determination of plasma CORT and blood ethanol levels. CORT was measured with the use of radioimmunoassay, and blood ethanol levels were determined with the use of gas chromatography. The results showed that although caffeine and ethanol delivered singly failed to augment plasma CORT levels, the combination of both drugs produced elevations in plasma CORT levels at 15 and 30 min. These findings were found to be unrelated to changes in ethanol metabolism as caffeine failed to alter blood ethanol levels within the period tested. It was argued that the present elevations in plasma CORT levels observed in animals administered caffeine and ethanol may play a role in the caffeine-induced elevations in ethanol drinking observed elsewhere.

Alcohol Drinking↗

PubMed2000

Relative taste thresholds for ethanol, saccharin, and quinine solutions in three strains of rats nonselected for ethanol: a comparative study.

C. P. Richter and K. H. Campbell (1940b) originally defined taste threshold as "the point at which the rats first indicated that they recognized a difference between the distilled water and the solutions" (p. 34). The present study sought to apply this simple behavioral measure to the investigation of strain differences in taste sensitivities, particularly with respect to predictive relationships in ethanol, saccharin, and quinine preference. Fawn-Hooded, Lewis, and Wistar rats were presented with gradual increments in concentration of ethanol (0.01-15%; C. P. Richter & K. H. Campbell, 1940a), saccharin (0.002-3%) or quinine (0.0001-0.0055). Results showed that although intake for saccharin was similar in all strains, consumption of ethanol and quinine differed among the groups. Although previous research has proposed that sweet preference is a promising behavioral marker for ethanol preference, these results suggested that bitter preference may be a more reliable predictor of ethanol preference in rats.

Alcohol Drinking↗

PubMed1999

Pneumocysterol [(24Z)-ethylidenelanost-8-en-3beta-ol], a rare sterol detected in the opportunistic pathogen Pneumocystis carinii hominis: structural identity and chemical synthesis.

Pneumocystis carinii pneumonia (PcP) remains among the most prevalent opportunistic infections among AIDS patients. Currently, drugs used clinically for deep mycosis act by binding ergosterol or disrupting its biosynthesis. Although classified as a fungus, P. carinii lacks ergosterol. Instead, the pathogen synthesizes a number of distinct Delta7, 24-alkylsterols, despite the abundance of cholesterol, which it can scavenge from the lung alveolus. Thus, the pathogen-specific sterols appear vital for organism survival and proliferation. In the present study, high concentrations of a C32 sterol were found in human-derived P. carinii hominis. The definitive structural identities of two C-24 alkylated lanosterol compounds, previously not reported for rat-derived P. carinii carinii, were determined by using GLC, MS, and NMR spectroscopy together with the chemical syntheses of authentic standards. The C31 and C32 sterols were identified as euphorbol (24-methylenelanost-8-en-3beta-ol) and pneumocysterol [(24Z)-ethylidenelanost-8-en-3beta-ol], respectively. The identification of these and other 24-alkylsterols in P. carinii hominis suggests that (i) sterol C-24 methyltransferase activities are extraordinarily high in this organism, (ii) 24-alkylsterols are important components of the pathogen's membranes, because the addition of these side groups onto the sterol side chain requires substantial ATP equivalents, and (iii) the inefficacy of azole drugs against P. carinii can be explained by the ability of this organism to form 24-alkysterols before demethylation of the lanosterol nucleus. Because mammals cannot form 24-alkylsterols, their biosyntheses in P. carinii are attractive targets for the development of chemotherapeutic strategies against this opportunistic infection.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Exposure to nicotine enhances acquisition of ethanol drinking by laboratory rats in a limited access paradigm.

Observations in humans suggest that the initial use of tobacco occurs in close temporal proximity to experimentation with alcohol. There have been relatively few research reports, however, examining possible interactions between these two agents. The present experiments examined the effect of nicotine exposure on the acquisition of ethanol drinking behavior in a limited access procedure. In experiment 1, rats were presented with 1-h access to ethanol solutions of increasing concentration for a period of 20 days. Subcutaneous injections of nicotine (0.6 or 1.2 mg/kg salt) or vehicle were administered 30 min prior to each ethanol presentation. Experiment 2 used a similar method, but rats were presented with water along with ethanol during the 1-h test session. Mecamylamine, a nicotinic receptor antagonist, was administered 30 min prior to the nicotine treatment. Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%. In the second experiment, mecamylamine was observed to block completely the nicotine-induced increase in ethanol drinking behavior. The findings suggest that exposure to nicotine can facilitate the acquisition of ethanol drinking behavior in naive rats and that this effect is mediated by nicotine's interaction at the nicotinic-cholinergic receptor.

Alcohol Drinking↗

PubMed1999

Environmental lighting has a selective influence on ethanol intake in rats.

The effect of lighting condition on levels of absolute ethanol intake were systematically examined in the present study. Wistar rats were exposed to one of three lighting conditions: constant light, constant dark, and a standard 12/12 light/dark cycle. The animals were acclimatized to lighting conditions for 2 weeks prior to ethanol (EtOH) acquisition with water and food available ad lib. EtOH was then presented in increasing concentrations from 2% (v/v; 95% with tap water) to 10% on alternate days in free choice with water. Immediately following the acquisition phase, a maintenance period was initiated that began with everyday presentations of 10% EtOH solution in free choice with water. After 10 days, lighting conditions for the constant light and dark groups were switched to normal lighting (12/12 light/ dark). EtOH and water intake were recorded for an additional 10 days. Rats exposed to constant light during EtOH acquisition and maintenance consumed less EtOH during the maintenance period than rats exposed to normal lighting conditions. When lighting conditions were switched to a normal cycle, water consumption increased significantly but EtOH intake did not change. Rats living in constant dark during EtOH acquisition and maintenance consumed less EtOH during the acquisition period when compared with rats living in normal lighting conditions. Unlike animals trained under constant lighting, switching to normal lighting conditions had no effect on EtOH or water intake. There were no differences in water consumption levels among the groups during acquisition and maintenance, suggesting a specificity of the effects of lighting condition on EtOH intake. The present study, therefore, has attempted to show that an environmental variable such as lighting may exert a selective influence on EtOH self-selection in rats.

Alcohol Drinking↗

PubMed1999

Cocaine and ethanol interaction in the conditioned taste aversion paradigm.

The aim of this study was to examine the relationship between cocaine and ethanol in a variant of the conditioned taste aversion (CTA) paradigm. The preexposure CTA procedure formed the basis of the following set of experiments. Experiments 1a and 1b assessed whether cocaine and ethanol were functionally related with overlapping stimulus properties as reflected in the preexposure CTA procedure. Male Wistar rats with restricted water access were preexposed to cocaine or ethanol for 3 consecutive days. Twenty-four hours after the last preexposure session, rats were conditioned to either ethanol or cocaine, respectively. The results of this set of experiments revealed a symmetrical interaction between cocaine and ethanol, where cocaine and ethanol effectively blocked CTA to one another. These findings suggested that there may be overlapping stimulus properties between cocaine and ethanol, which may be detected in this procedure.

Animals↗

PubMed1999

Stress enhances the response to reward reduction but not food-motivated responding.

The effect of a single exposure to foot shock stress on runway responding for food reinforcement was assessed in animals trained and tested with the same or changed reinforcement magnitude. Foot shock (30 1-s shocks, 1.0 mA) exerted no impact on runway responding in animals trained and tested with the same level of reinforcement magnitude regardless of the absolute level of reinforcement magnitude (i.e., either 15 pellets or 1 pellet). Similarly, foot shock exerted no impact on runway responding in animals trained with a small magnitude of reinforcement but tested with an increased magnitude of reinforcement. In contrast, foot shock enhanced the increase in runway latencies produced by a reduction in reinforcement magnitude. Because reductions in reinforcement magnitude are known to be aversive for animals, these data indicate that foot shock stress can alter the behavioral response to an aversive stimulus without disrupting behavioral responding for an appetitive reinforcer. They also suggest that stressor-induced alterations in appetitively motivated behaviors may be secondary to alterations in sensitivity to subtle aversive stimuli rather than by directly altering appetitive motivation.

Animals↗

PubMed1999

Nicotine and ethanol interaction on conditioned taste aversions induced by both drugs.

The present study was designed to explore the interactive effects of nicotine and ethanol in the pretreatment and preexposure conditioned taste aversion (CTA) paradigm. The first experiment examined the effects of ethanol pretreatment on a nicotine induced CTA. The second experiment examined the effects of nicotine pretreatment on an ethanol CTA. The results of these two experiments revealed an asymmetrical interaction between ethanol and nicotine. Although nicotine pretreatment blocked an ethanol induced CTA, ethanol pretreatment merely attenuated a nicotine-induced CTA. These findings demonstrated that ethanol and nicotine interact pharmacologically in a unidirectional fashion, suggesting some unique and unshared pharmacological properties of each agent. The third experiment of this study examined the effects of preexposure with ethanol on a nicotine-induced CTA, while the fourth experiment examined the effects of preexposure with nicotine on an ethanol-induced CTA. These results revealed a symmetrical interaction between ethanol and nicotine in that both agents equally blocked CTA to one and the other. In contrast to the pretreatment CTA paradigm, these results suggested that both ethanol and nicotine appear to be functionally related and share common stimulus properties. Taken together, the present study demonstrates that while ethanol and nicotine are functionally related, they may also be endowed with unique unshared properties.

Analysis of Variance↗

PubMed1999

The effects of the GABA(B) agonist baclofen on the temporal and structural characteristics of ethanol intake.

The present study examined the behavioral processes mediating the influence of the GABA(B) agonist baclofen on the maintenance of voluntary ethanol intake. Long-Evans rats were randomly assigned to two groups, one receiving baclofen (10 mg/kg, IP) and the other an equal volume of saline. Subjects were presented with a free choice of ethanol (10% v/v) and water immediately following drug injections, which occurred every other day. The results demonstrated that baclofen treatment resulted in an overall increase in the intake of absolute ethanol but failed to influence the intake of water. In contrast, food intake was substantially attenuated as evidenced by a decrease in the number of pellets consumed in subjects treated with baclofen. A microanalysis of the patterns of food and fluid bouts indicated that the enhanced ethanol intake was primarily a function of an increase in the frequency of ethanol bouts. In contrast, the decrease in food intake appeared to be a reflection of a decrease in the size of the food meals but not their frequency. An analysis of the temporal pattern of intake over the 23-h test sessions indicated that baclofen treatment produced a biphasic effect on ethanol intake with a slight decrease in intake during the first hour following treatment. Baclofen-treated animals then were observed to consume greater amounts of ethanol than did saline controls throughout the remainder of the dark cycle as well as into the light cycle. Although ethanol intake gradually decreased in controls throughout the light cycle, baclofen-treated subjects maintained a consistent level of intake throughout this period. Furthermore, there was a clear dissociation between the temporal pattern of ethanol intake and that of food and water, as intake of the latter substances was shown to decrease during the first hour following injection, but unlike with ethanol, no increase in intake was observed during the remainder of the test session. The nature of the effects of baclofen observed in the present study would suggest that the GABA(B) receptor system may not play a central role in the mediation of voluntary ethanol intake.

Alcohol Drinking↗