Biomedical subjects

C M Aragon

Publications and source records attributed to C M Aragon.

At least 37 records · Page 2Linked to original sources

PubMed1992

Effect of taurine on ethanol-induced changes in open-field locomotor activity.

In the present investigation we questioned whether taurine antagonized the effects of ethanol on motor activity measured in the open field. Ten minutes following simultaneous administration (IP) of ethanol (1.0, 1.5, 2.0 and 2.5 g/kg) or saline and taurine (30, 45 and 60 mg/kg) or saline, mice were placed in open field chambers and locomotor activity was measured during a 10 min testing period. A significant interaction was found between taurine and ethanol. Taurine-treated mice displayed lower motor excitation with the 1.0 g/kg dose of ethanol than the saline group treated with the same dose of ethanol. However at the 2.0 g/kg ethanol dose, taurine-treated mice demonstrated higher motor activity than the saline treated mice, once again, treated with the same dose of ethanol. No differences in blood ethanol levels were observed between the two groups. In a second study, taurine administration (30, 45 and 60 mg/kg) did not show any effect on d-amphetamine-induced enhancement of locomotor activity (1, 2, and 3 mg/kg). Data from this study demonstrated an interaction between taurine and ethanol in their effect on locomotor activity in the open field.

Animals↗

PubMed1992

The effect of 3-amino-1,2,4-triazole on voluntary ethanol consumption: evidence for brain catalase involvement in the mechanism of action.

The effects of the catalase inhibitor, 3-amino-1,2,4-triazole (AT), on maintenance of voluntary consumption of ethanol was tested in male Long-Evans rats. AT produced a dose-dependent reduction in ethanol intake but did not affect total fluid consumption. AT also produced a dose-dependent inhibition of brain catalase lasting throughout the drinking period. These results suggest a role for brain catalase in determining the level of ethanol intake in rats.

Alcohol Drinking↗

PubMed1991

Dose- and time-dependent effect of an acute 3-amino-1,2,4-triazole injection on rat brain catalase activity.

The results presented in this study demonstrate a progressive inhibition of rat brain catalase activity by AT in vivo. Furthermore, the inhibition of brain catalase by AT demonstrates the presence of hydrogen peroxide in brain, since AT inhibits catalase in the presence of this compound. The rate of inhibition of catalase seems to be dependent upon the rate by which H2O2 is generated. A time course study showed slower onset of the inhibition of brain as compared to liver catalase, possibly reflecting tissue hydrogen peroxide levels or, alternatively, a rate-limiting penetration of AT into brain and into the catalase compartment. The presence of AT in brain was confirmed over the time period of the observed inhibition of brain catalase. Catalase inhibitors are of particular interest in the study of the physiological role of catalase. This study further supports the use of AT in investigations designed to further understand the role of brain catalase.

Amitrole↗

PubMed1991

Ethanol-induced CTA mediated by acetaldehyde through central catecholamine activity.

The possible involvement of catecholamines (CA) in the mediation of acetaldehyde's conditioned taste aversion (CTA) was examined by testing the effects of alpha-methyl-para-tyrosine (AMPT, a tyrosine hydroxylase inhibitor) on the CTAs produced by acetaldehyde. AMPT blocked the acquisition of the CTA normally produced by a low dose of acetaldehyde (0.2 g/kg), but had no significant effect on CTA produced by a high dose of acetaldehyde (0.3 g/kg). In a second study, acetaldehyde's role in the CTA produced by ethanol was investigated using the pre-exposure conditioned taste aversion paradigm. Pre-exposure to acetaldehyde (both doses) blocked the ethanol CTAs but when pre-exposure with acetaldehyde was coupled with AMPT, only the larger dose of acetaldehyde blocked the ethanol aversion. These results suggest that while the CTA to the low dose of acetaldehyde may be primarily central and catecholamine-mediated, the mechanism underlying the high dose CTA is probably peripheral and emetic in nature. These findings support the conclusion that acetaldehyde may be mediating many of the actions of ethanol.

Acetaldehyde↗

PubMed1991

Involvement of endogenous opioid mechanisms in the interaction between stress and ethanol.

The involvement of endogenous opioid mechanisms in the interaction between stress and ethanol was investigated in the rat. Animals were pretreated with naltrexone (10 mg/kg) or saline 3 h before a second injection consisting of ethanol (1.0 g/kg) or saline. They were then restrained for 15 or 60 min or left in home cages for an equivalent amount of time. After restraint, animals were either subjected to an open-field test or decapitated to collect blood for corticosterone determinations. Locomotor depression was found to be induced by 15 but not 60 min restraint. In naltrexone-treated animals, however, 60 min restraint was also found to induce locomotor depression. Ethanol pretreatment was found to block the locomotor depression induced by 15 min restraint. Such an interaction was in turn antagonized by naltrexone. In the 15 min condition, stress and ethanol were also found to interact in their effects on plasma levels of corticosterone. Naltrexone did not alter any effects of the stressors on corticosterone levels. These results provide support for the involvement of endogenous opioid mechanisms in the interaction of stress and ethanol at a behavioural level.

Animals↗

PubMed1991

Effect of 3-amino-1,2,4-triazole on ethanol-induced narcosis, lethality and hypothermia in rats.

It has been proposed that ethanol can be oxidized in brain via the peroxidatic activity of catalase and that centrally formed acetaldehyde may mediate several of the psychopharmacological actions of ethanol. The present study was designed to investigate the role of brain catalase in the mediation of ethanol-induced narcosis, hypothermia and lethality in rats. Rats were pretreated with the catalase inhibitor 3-amino-1,2,4-triazole (AT) or saline. Five hours later, animals in each pretreatment group received IP injections of ethanol (3 or 4 g/kg). Ethanol-induced narcosis was significantly attenuated in AT-pretreated rats compared to the saline control group. As well, AT pretreatments reduced significantly the lethal effect of these ethanol doses. However, AT-pretreated ethanol-injected animals significantly reduce their body temperature as compared to the saline-ethanol animals. Blood ethanol determinations revealed that AT did interfere with ethanol metabolism. AT inhibits significantly brain catalase activity at all doses used in this study. The results indicate a role for brain catalase in ethanol effects. Furthermore, they suggest that catalase may be involved in the oxidation of ethanol in brain and that centrally formed acetaldehyde may play a role in ethanol-induced narcosis and lethality, but not hypothermia.

Amitrole↗

PubMed1991

Studies on ethanol-brain catalase interaction: evidence for central ethanol oxidation.

The purpose of the present investigation was to further study the relationship between ethanol and brain catalase in vivo. Rats were pretreated intraperitoneally (ip) with varying doses of ethanol or saline 30 min prior to administration of cyanamide (0.68 mmol/kg; ip), 4-hydroxypyrazole (1 mmol/kg; ip) or saline. Rat tissues were perfused in situ under ether anaesthesia. Brain catalase activity was measured using the Clark electrode. Results confirmed inhibition of brain catalase activity by cyanamide and 4-hydroxypyrazole. Ethanol protected catalase from cyanamide and 4-hydroxypyrazole inactivation in a dose-related manner. In a second study, homogenates from perfused brains were incubated in the presence of glucose and glucose oxidase with ethanol or saline and cyanamide or saline. Cyanamide was shown to inhibit the catalase activity in vitro in a dose-related manner. Ethanol prevented this inhibition of catalase when added to the incubation medium prior to cyanamide. These data suggest a competition between ethanol and inhibitors for the H2O2-catalase compound. They also confirm the presence and generation of H2O2 in the rat brain in vivo, and overall seem to support the notion that centrally formed acetaldehyde via brain catalase may be responsible for some of the psychopharmacological actions of ethanol.

Acetaldehyde↗

PubMed1990

Effects of ethanol on locomotor depression and corticosterone release induced by restraint-stress: support for a stress-ethanol interaction.

The interaction between restraint-stress and ethanol was investigated in the rat. The effects of ethanol pretreatment (0.0, 1.0, 1.5, 2.0 g/kg, 20% v/v) on locomotor depression and corticosterone release induced by restraint-stress (15, 60 min) were measured. Restraint durations of 15, 30, 90 and 120 min were found to decrease locomotor activity while animals restrained for 60 min did not differ from home cage controls. All restraint durations induced a significant increase in plasma levels of corticosterone. Locomotor activity counts of ethanol-pretreated (1.0, 1.5, 2.0 g/kg; 20% v/v) animals restrained for 15 min were not found to be lower than those of ethanol-pretreated animals remaining in home cages. Ethanol pretreatment did not differentially affect the locomotor activity of restrained or home cage animals in the 60-min condition. Plasma corticosterone levels of ethanol-pretreated animals restrained for 15 min were identical to those of ethanol-pretreated home cage controls. However, ethanol-pretreated animals restrained for 60 min demonstrated plasma corticosterone levels higher than those obtained by ethanol pretreatment or 60-min restraint alone. Blood ethanol levels were not found to be different between ethanol-control and ethanol-stress animals. These results provide support for a stress-ethanol interaction. They also suggest a differential interaction of ethanol with different intensities of stress.

Animals↗

PubMed1990

Stress-ethanol interaction: involvement of endogenous opioid mechanisms.

Stress effects vary with different environmental situations or stress intensities. The effects of restraint stress on locomotion and or corticosterone were examined. Rats were restrained for 0, 15, 30, 60, 90 or 120 min, subsequent locomotion was measured for 10 min. Rats were also sacrificed for corticosterone determinations. Restraint stress affects both variables. Locomotion was recorded in rats pretreated with naltrexone or vehicle prior to restraint of 15 or 60 min. Naltrexone influenced the effects of stress differentially. It did not affect the results following 15 min of restraint but suppressed locomotion after 60-min restraint to a level comparable to that found after 15 min. Treatment with ethanol (1.0, 1.5, 2.0 g/kg) prior to 15 or 60 min of restraint resulted in the prevention of hypomotility induced by 15-min stress. It also interacted nonadditively with 15-min stress on corticosterone release. No such interaction occurred with 60 min stress. Also, naltrexone made it possible to block the effect of ethanol on restraint-induced hypomotility. Results describe stress as a nonunitary concept. Its effects tend to vary with its duration. The differential interaction of stress with naltrexone and ethanol depending on its duration supports the above notion. Results further suggest recruitment of opioid systems in long duration stress (60 min).

Animals↗

PubMed1989

Effects of 3-amino-1,2,4-triazole on ethanol-induced open-field activity: evidence for brain catalase mediation of ethanol's effects.

The role of brain catalase in the mediation of ethanol's effects on motor activity was investigated. Male Long-Evans rats were pretreated with i.p. injections of the catalase inhibitor, 3-amino-1,2,4-triazole (AT) (1 g/kg) or saline (S). Four hours later, animals in each group received i.p. injections of one of two doses of ethanol (ETOH) [1.0 g/kg (E1) or 2.0 g/kg (E2)] or one of two volumes of distilled water (W1 or W2). Ten minutes after the administration of these agents, animals were placed in open-field chambers and motor activity was recorded during a 10-min testing period. Results indicated that the motor depression produced by 2.0 g/kg of ETOH was significantly attenuated in AT pretreated rats (group AT-E2). AT pretreatment, however, had no effect on motor activity for subjects injected with 1.0 g/kg ethanol or water. Total brain catalase activity in AT-pretreated animals was 15% of control animals. No differences in blood ethanol levels were observed between AT- and S-pretreated animals. An interaction between ethanol and AT at the level of the central nervous system is suggested. The results of the present study suggest that brain catalase activity may be involved in ethanol's effects. They also provide further support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects.

Amitrole↗

PubMed1988

Catalase activity measured in rats naive to ethanol correlates with later voluntary ethanol consumption: possible evidence for a biological marker system of ethanol intake.

Catalase activity in blood collected from young rats naive to ethanol (65 days) was significantly and positively correlated with later voluntary consumption of ethanol. Catalase activity levels were also correlated with catalase activity in brain and blood sampled after exposure to ethanol. The results obtained in the present study extend and confirm earlier findings (Aragon et al. 1985c) that brain catalase activity and voluntary ethanol intake are unidirectionally and causally related. The results also suggest that brain catalase activity may be part of an enzymatic system controlling the production and elimination of acetaldehyde in brain. This system may be a biological marker system mediating the affinity of organisms to ingest ethanol.

Alcohol Drinking↗

PubMed1987

Alterations in brain aldehyde dehydrogenase activity modify ethanol-induced conditioned taste aversion.

The role of peripherally and centrally acting acetaldehyde in ethanol-induced conditioned taste aversion (CTA) was investigated using various enzyme manipulations. Cyanamide, an aldehyde dehydrogenase inhibitor (ALDH) elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Under both treatment conditions brain and liver ALDH activity is inhibited. Water-deprived rats were pretreated 4 hr prior to fluid presentation with intraperitoneal injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C), or 4-methylpyrazole + cyanamide (4MP+C). Subsequently, animals were presented with a novel saccharin solution followed immediately by intraperitoneal injection of one of three doses of ethanol (0.4, 0.8, or 1.2 g/kg) or saline vehicle on four occasions. Results suggested that animals pretreated with cyanamide (groups S+C and 4MP+C) drank significantly less saccharin after conditioning with a subthreshold dose of ethanol (0.4 g/kg) in comparison to groups S+S and 4MP+S. Moreover, at the conditioning dose of 1.2 g/kg, cyanamide-treated animals demonstrated an attenuation of CTA compared to the other two groups. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral acetaldehyde accumulation. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of ethanol-induced CTAs. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.

Acetaldehyde↗

PubMed1987

Corticosterone response to an acute dose of ethanol in naive and ethanol experienced rats.

The corticosterone response to an acute dose of ethanol (2 g/Kg, i.p.) was measured in the same rats in three different occasions: prior to, immediately following exposure to ethanol in a free choice self-administration paradigm and after a 15 day period of abstinence following exposure. Corticosterone was measured fluorometrically from tail blood samples collected 30 minutes following the ethanol injection. Blood ethanol levels were determined by gas chromatography. Mean plasma corticosterone and ethanol levels following the acute ethanol challenge were not significantly different in the three tested periods. A significant negative correlation between plasma corticosterone levels in the naive state and subsequent levels of individual voluntary ethanol intake was obtained. No apparent relationship was observed, however, between the same levels of ethanol consumption and the corticosterone response in these animals after ethanol exposure or exposure with abstinence. These data suggest that levels of ethanol intake may be related to the initial response to acute ethanol of the adrenal-pituitary axis. If so, this acute response to ethanol may be used to predict subsequent levels of ethanol intake.

Alcohol Drinking↗

PubMed1987

Alterations in brain aldehyde dehydrogenase activity modify the locomotor effects produced by ethanol in rats.

The role of brain aldehyde dehydrogenase (ALDH) and acetaldehyde in mediating ethanol-induced locomotor activity was investigated using several enzyme inhibitors. Cyanamide, an ALDH inhibitor elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole, an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Two hr prior to testing locomotor activity in open field boxes, 111 male Long Evans rats were pretreated with i.p. injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C) or 4-methylpyrazole + cyanamide (4MP+C). Subjects then received i.p. injections of one of three doses of ethanol (0.4, 0.8 or 1.2 gm/kg) or saline vehicle one minute prior to testing in the open field and locomotor activity was recorded for a 10 min period. Locomotor activity of animals pretreated with cyanamide (S+C and 4MP+C) was significantly depressed compared to groups S+S and 4MP+S particularly at the two lower doses tested. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral accumulation of acetaldehyde. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of locomotor effects produced by ethanol. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.

Acetaldehyde↗

PubMed1986

Acetaldehyde may mediate reinforcement and aversion produced by ethanol. An examination using a conditioned taste-aversion paradigm.

Groups of water-deprived rats were exposed to acetaldehyde, ethanol or vehicle control. On the conditioning day, the animals were first presented with a solution of saccharin after which the animals that were exposed to acetaldehyde received ethanol and those exposed to ethanol received acetaldehyde. Saccharin was again presented on three more occasions (testing days) without injection of drug. Using the percentage change in saccharin consumed from the first presentation as a measure of aversion, it was found that exposure to acetaldehyde blocked the taste aversion conditioned by ethanol. Animals exposed to ethanol showed no aversion to the saccharin which was paired with a small dose of acetaldehyde, indicating a symmetrical relationship between ethanol and acetaldehyde at this dose. However, exposure with ethanol did not block the aversion produced by conditioning with larger doses of acetaldehyde. These results suggest that the mechanism underlying the smaller dose of the taste aversion conditioned with acetaldehyde may be central while the mechanism underlying the larger dose is probably peripheral.

Acetaldehyde↗

PubMed1985

Blockade of ethanol induced conditioned taste aversion by 3-amino-1,2,4-triazole: evidence for catalase mediated synthesis of acetaldehyde in rat brain.

This investigation seeks to present evidence for the oxidation of ethanol in the brain via the peroxidatic activity of catalase and simultaneously provide evidence for the role of central acetaldehyde (ACH) in the mediation of an ethanol-induced conditioned taste aversion (CTA). Ethanol is capable of inducing a conditioned taste aversion. Pretreatment with the catalase inhibitor, 3-amino-1,2,4-triazole (AT), shows an attenuation of this ethanol-induced CTA. Animals receiving ethanol injections showed a CTA to a novel solution paired with a drug administration, while ethanol injected animals pretreated with AT did not show a CTA to ethanol administration. This effect of AT appears to be specific to the effects of ethanol as CTA's to morphine and lithium chloride were not affected by AT pretreatment. Peripheral levels of ethanol were the same in all animals regardless of pretreatment indicating that AT had no effect on peripheral levels of ethanol. These data increase support for the notion that acetaldehyde is produced directly in the brain and that it may be the agent mediating some of the psychopharmacological properties of ethanol.

Acetaldehyde↗

PubMed1985

A time-dependent biphasic effect of an acute ethanol injection on 3-methoxy 4-hydroxyphenylethylene glycol sulfate in rat brain.

The present experiment demonstrated that acute administration of ethanol appeared to have a biphasic effect on the accumulation of 3-methoxy-4-hydroxyphenylethylene glycol sulfate (MHPG-SO4) in rat brain. The magnitude of these alterations in MHPG-SO4 levels was also observed to be highly correlated with peripheral blood ethanol levels. Since levels of MHPG-SO4 are considered to be an index of noradrenergic activity, the findings suggest that ethanol may affect norepinephrine activity in a specific dose- and time-dependent manner. These results are discussed in reference to previous reports describing apparent divergent effects on norepinephrine. Possible mechanisms for the biphasic actions are also suggested.

Animals↗

PubMed1984

Higher correlation of ethanol consumption with brain than liver aldehyde dehydrogenase in three strains of rats.

Voluntary ethanol consumption and high Km (mM range) brain and liver aldehyde dehydrogenase (ALDH) activity were measured in male rats of the Long-Evans, Wistar and Sprague-Dawley strains. The total amounts of ethanol consumed by the three strains did not differ significantly, nor did the levels of cerebral ALDH activity. Levels of brain ALDH did not differ as a function of ethanol exposure and across strains. Levels of ethanol consumption correlated better with levels of brain than liver aldehyde-oxidizing capacity, which were tested separately for each strain and also combining all the animals. Inherent variation in brain ALDH may be a biochemical counterpart of observed differences in voluntary ethanol intake within strains.

Alcohol Drinking↗