PubMed Health⌕ Search

Biomedical subjects

A D Lê

Publications and source records attributed to A D Lê.

At least 19 recordsLinked to original sources
PubMed1992

Influence of intoxicated practice on the development of acute tolerance to the motor impairment effect of ethanol.

The influence of practice while under intoxication was tested on the development of acute tolerance to the motor impairment effect of ethanol. In experiment 1, the motor impairment effect induced by an IP injection of 1.8 g/kg ethanol was quantified after various intervals in separate groups of animals. Lower impairment scores were observed in rats tested at 30 and 45 min after ethanol administration than in those tested at 15 min. In group that was tested repeatedly after ethanol administration, intoxication decreased more rapidly and to a greater extent. The same phenomenon was observed in experiment 2 when a higher dose of ethanol (2.2 g/kg) and later testing (60-180 min after ethanol administration) were employed. To maintain constant blood ethanol levels, those tested at later times received a supplementary dose of ethanol. Impairment scores were lower in rats tested at later times than in those tested earlier. Again, the impairment scores for the practice group decreased more rapidly and to a greater extent. Blood ethanol levels among various groups were essentially the same. Acute tolerance to ethanol can develop without opportunity for practice while under intoxication. Intoxicated practice, however, can facilitate acute tolerance development.

Animals↗
PubMed1992

Differential development of acute tolerance to the motor impairment and anticonvulsant effects of ethanol.

The development of acute tolerance to the motor impairment and anticonvulsant effects of ethanol was examined. Acute tolerance to the motor impairment effect of ethanol was shown by a decrease in the degree of intoxication, as measured on the moving belt task, at higher blood ethanol levels ranging from 206 to 256 mg/dl. There was no evidence of acute tolerance to the anticonvulsant effect of ethanol in rats tested over the same time period. These results indicate that, like chronic tolerance, acute tolerance to ethanol develops at different rates for different effects of the drug. The fact that chronic tolerance to the anticonvulsant effect of ethanol has been well documented raises doubts about the assumption that similar physiological changes underlie acute and chronic tolerance to a drug effect, and support the idea that the relationship between acute and chronic tolerance is more complex than previously thought.

Amygdala↗
PubMed1992

Effects of chronic treatment with ethanol on the development of cross-tolerance to other alcohols and pentobarbital.

The development of cross-tolerance to various alcohols and pentobarbital was examined in ethanol (EtOH)-treated mice. Chronic EtOH treatment (dosage rising in steps from 3.5-4.5 g/kg i.p. daily during a 23-day period) produced tolerance to its hypnotic effect. Such tolerance was seen as a reduction in the duration of loss of righting reflex (LRR), as well as higher blood EtOH levels at the offset of LRR, in EtOH-treated mice as compared to saline-treated controls. Cross-tolerance was shown by shifts in dose-response curves for the LRR induced by n-propanol and t-butanol. Such treatment, however, did not confer functional cross-tolerance to n-butanol and pentobarbital. Because n-butanol and pentobarbital are more lipid-soluble, whereas EtOH, n-propanol and t-butanol have low degrees of lipid solubility, the development of cross-tolerance among these sedative-hypnotic drugs might be related to their relative degrees of lipid solubility.

1-Butanol↗
PubMed1991

Chronic selective blockade of mu opioid receptors produces analgesia and augmentation of the effects of a kappa agonist.

We have previously demonstrated that, when administered chronically, naloxone and naltrexone have the paradoxical effect of producing analgesia in rats. In this study, rats treated chronically with intracerebroventricular (i.c.v.) microinjections, and mice treated chronically with subcutaneous (s.c.) injections of naloxone or beta-funaltrexamine (beta-FNA) developed analgesia on daily hot plate tests. There was not drug effect on the first day of hot plate testing, but significant increases in paw lick latency developed over subsequent acquisition sessions for animals treated with beta-FNA or naloxone. An augmented analgesic response to a 5 mg/kg s.c. injection of the kappa opioid agonist, U50-488H, was observed in mice previously treated with naloxone or beta-FNA. The primary findings of the present study were: (1) chronic blockade of mu opioid receptors is sufficient to produce analgesia on repeated hot plate tests in both rats and mice; (2) chronic blockade of mu receptors in the presence of stressful stimuli results in augmentation of kappa agonist-induced analgesia; and (3) the phenomenon of opioid blockade-induced analgesia (OBA) occurs in mice as well as rats.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1991

Role of central versus peripheral opioid receptors in analgesia induced by repeated administration of opioid antagonists.

Although analgesia induced by blockade of opioid receptors has been well established, it is still unknown whether its development is mediated by the blockade of centrally located opioid receptors. Therefore, rats were treated with either systemically or ICV applied naloxone or quaternary naltrexone (QN), an opioid antagonist that does not easily penetrate the blood-brain barrier. Following antagonist administration, each animal was tested for paw lick latency on a 51 degrees C hot plate. Hot plate testing and drug injections were carried out for 4 consecutive days. Rats treated with ICV microinjections of QN or naloxone displayed paw lick latencies that were significantly longer than those observed in control animals. In contrast, rats treated with SC injections of QN did not show any increase in paw lick latency, whereas rats treated with SC injections of naloxone displayed paw lick latencies that were significantly longer than those of control rats. These results are consistent with the hypothesis that the blockade of central opioid receptors underlies the development of an analgesic response.

Analgesia↗
PubMed1990

Role of initial sensitivity and genetic factors in the development of tolerance to ethanol in AT and ANT rats.

The role of initial sensitivity and genetic factors in the development of tolerance to ethanol were examined in rats selected for low (AT) and high (ANT) sensitivity to the motor impairment effect of ethanol. Following chronic ethanol treatment (5 g/kg PO, daily for 20 days), the AT and ANT rats acquired tolerance to the motor impairment effect of ethanol at a similar rate. The AT rats, however, acquired tolerance to the hypothermic effect of ethanol at a higher rate than the ANT rats. Such ethanol treatment did not produce any metabolic tolerance to ethanol in these animals. Since there is no difference in the initial response to the hypothermic effect of ethanol between the AT and ANT rats, the observed differences in the rate of tolerance development might be related to a direct genetic factor. The similar rate of tolerance development to the motor impairment effect of ethanol between the two lines was attributed to an interaction between an indirect (initial sensitivity) and a genetic factor in tolerance development.

Animals↗
PubMed1990

Factors regulating ethanol tolerance.

Ethanol tolerance is a complex phenomenon. Its development is governed by pharmacological and behavioural, as well as genetic factors. The doses of ethanol employed and the duration of ethanol treatment are important pharmacological variables. Behavioural factors such as experience of intoxication and Pavlovian conditioning may also affect the development or manifestation of ethanol tolerance. Genetic factors can influence the development of tolerance directly or/and indirectly through its influence on the initial sensitivity to ethanol. The relevance and implication of tolerance, particularly conditioned tolerance in alcohol abuse and alcoholism, are discussed.

Alcoholic Intoxication↗
PubMed1989

The AA and ANA rat lines, selected for differences in voluntary alcohol consumption.

The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.

Alcohol Drinking↗
PubMed1989

The contribution of environmental cues to cross-tolerance between ethanol and pentobarbital.

The contribution of Pavlovian conditioning of environmental cues has been studied in relation to tolerance to ethanol-induced hypothermia and cross-tolerance to pentobarbital. Two groups of 12 male Sprague-Dawley rats were exposed every other day to a distinctive set of environmental cues paired with an IP injection of either ethanol 2.5 g/kg or an equivalent volume of isotonic saline. On alternating non-drug days, both groups received saline in the animal room. When they were tested for tolerance to the hypothermic effect of ethanol 2.5 g/kg and cross-tolerance to pentobarbital 25 mg/kg in each environment, tolerance and cross-tolerance in the ethanol-treated group were significantly more pronounced in the ethanol-paired environment than in the saline-paired environment. This indicates the importance of a conditional factor in tolerance and cross-tolerance in this paradigm. Determination of blood levels of ethanol and pentobarbital at various times after injection indicated that conditioned tolerance and cross-tolerance can be explained in part by dispositional factors.

Animals↗
PubMed1989

Enhancement of naloxone-induced analgesia by pretreatment with morphine.

Recently there have been demonstrations of a form of analgesia in rats that depends on the repeated administration of an opiate antagonist for its occurrence. The mechanism of this naloxone-induced analgesia (NIA) is not clear. This experiment tested the hypothesis that the relationship between behavioral effects of previous experience with opiate agonists and antagonists would be reciprocal with respect to analgesia. Consistent with such an hypothesis, prior exposure to morphine increased sensitivity to the effect of naloxone as measured by the rate of acquisition of NIA. Although receptor functions were not measured, reciprocal changes in the regulation of opiate receptors by opiate receptors by opiate agonists and antagonists may underlie the behavioral effects observed in this experiment.

Analgesia↗
PubMed1989

Naloxone-induced analgesia: effects of the benzodiazepine antagonist Ro 15-1788.

Repeated exposure to pain under the influence of the opiate antagonists naloxone and naltrexone leads to the recruitment of substantial analgesia as measured by paw-lick latency on the hot-plate test (4,11). One hypothesis to explain this naloxone-induced analgesia (NIA) is that nociceptive stimulation in the face of opiate blockade becomes stressful enough to activate an analgesic adaptation that otherwise would not occur. This hypothesis was examined in two experiments by the administration of a benzodiazepine antagonist with anxiogenic properties (Ro 15-1788, in a dose of 10 mg/kg) in conjunction with repeated administrations of naloxone (5 mg/kg). One experiment incorporated defecation as a relatively direct measure of stress. Ro 15-1788 reliably augmented NIA. Defecation was increased by naloxone alone and in combination with Ro 15-1788. Overall, the results were most consistent with the hypothesis that NIA is a form of stress-induced analgesia that is at least partly nonopiate in nature.

Analgesia↗
PubMed1988

Characteristics of ethanol tolerance in alcohol drinking (AA) and alcohol avoiding (ANA) rats.

The development of tolerance to ethanol was examined in two rat lines selected for high (AA) and low (ANA) ethanol consumption. In the first experiment, the acquisition of tolerance to the motor-impairment, hypothermic and hypnotic effects of ethanol produced by daily treatment with 5 g/kg ethanol for a period of 24 days was examined. Tolerance to these effects of ethanol was observed in the AA rats while marginal or no tolerance was demonstrated in the ANA rats. In the second experiment the development of rapid tolerance to the hypothermic and hypnotic effects of ethanol was examined. The hypothermic and hypnotic responses to IP injection of 3.5 g/kg ethanol were found to be attenuated in the AA but not the ANA rats by a single equivalent ethanol injection given 24 h earlier. These results suggest some relationship between the capacity to develop tolerance and voluntary ethanol intake.

Alcohol Drinking↗
PubMed1988

Effect of raphe lesions on the development of acute tolerance to ethanol and pentobarbital.

The effect of electrolytic lesions in the median and dorsal raphe nuclei was tested on acute tolerance development to ethanol and pentobarbital in the rat, as measured by motor impairment on the moving belt test. Acute tolerance to ethanol (1.7 g/kg, IP) or pentobarbital (17.5 mg/kg, IP) was monitored at 12.5, 25, or 50 min in separate subgroups tested only once each. One week of recovery was allowed between ethanol and pentobarbital tests. Median raphe lesions delayed the development of acute tolerance, whereas dorsal raphe lesions produced a negligible effect. These results were seen with both ethanol and pentobarbital. The mesolimbic 5-HT pathway from the median raphe nucleus is important in the development of acute tolerance to ethanol and pentobarbital, as was shown to be the case previously for chronic tolerance.

Animals↗
PubMed1988

"Paradoxical" analgesia induced by naloxone and naltrexone.

Analgesic effects of pellet implantation of the opiate antagonists naloxone and naltrexone and of chronic administration of naloxone by subcutaneous injection were examined. Rats were implanted with a slow-release pellet containing 10 mg naloxone or 10 mg naltrexone and tested for paw-lick latency on a hotplate apparatus. Controls were implanted with placebo pellets or given saline injections as appropriate. There were five test trials at intervals up to 72 h after implantation of naloxone and up to 120 h after the implantation of naltrexone. In a separate experiment, 5 mg/kg naloxone was injected; there were single trials on 5 consecutive days. All drug-treated animals displayed clear and substantial analgesia by their second test trial. This "paradoxical" analgesia was gradually reversed in the pellet-implant groups as tissue levels of the antagonists declined, but increased progressively with each trial involving injections. It was hypothesized that blockade of endogenous opiates by antagonists resulted in a form of "super-pain" on the hotplate, which in turn activated a normally redundant "backup" analgesic system. The results with naloxone injections show that unlike opiate-mediated analgesia, this hypothetical system is resistant to tolerance.

Analgesics↗
PubMed1988

Effect of chronic pentobarbital treatment on the development of cross-tolerance to ethanol and barbital.

Recently, we reported that a chronic regimen of ethanol by intubation, which produced clear tolerance to ethanol-induced hypothermia, ataxia and sleep, produced only a marginal degree of cross-tolerance to these effects of pentobarbital. The present experiments were designed to test the reverse process by examining cross-tolerance to pentobarbital after chronic pretreatment with ethanol, chronic pentobarbital treatment by gavage conferred clear cross-tolerance to both barbital- and ethanol-induced hypothermia, ataxia and sleep. In a separate experiment, cross-tolerance to barbital- and ethanol-induced hypothermia and ataxia was demonstrated over a wide range of test doses. Determination of ethanol blood levels as well as a complete time course of absorption, distribution and elimination of ethanol suggested that pharmacokinetic alterations may play a role in the development of cross-tolerance to ethanol in pentobarbital-treated subjects. The asymmetry of cross-tolerance raises the possibility that pentobarbital and ethanol invoke tolerance by mechanisms that are not wholly identical. This possibility requires further exploration. Conceivably the actions of ethanol which mediate the measured effects form a subset of a larger range of pentobarbital actions that could provide a stronger stimulus to tolerance development.

Animals↗
PubMed1987

Role of Pavlovian conditioning in the development of tolerance and cross-tolerance to the hypothermic effect of ethanol and hydralazine.

The role of Pavlovian conditioning in the development of tolerance to the hypothermic effect of ethanol and of cross-tolerance to hydralazine was investigated. In the first study, two groups of rats were treated on alternate days with ethanol (2 or 4 g/kg, respectively, IP) in a novel and distinctive environment (DR). On the non-alcohol days, they received saline in the home room (HR). A control group received saline in both environments. Tolerance to the hypothermic effect of ethanol in the DR was demonstrable in both the 2 and 4 g/kg treatment groups. Tolerance in the HR, however, was observed only in the 4 g/kg treated group. Cross-tolerance to the hypothermic effect of hydralazine was observed for both ethanol-treated groups in the DR but not in the HR. In the second study, ethanol treatment was carried out by daily intubation with 6 g/kg ethanol in the home cage. Tolerance to ethanol-induced hypothermia was demonstrated either in the home cage or in a novel environment. This treatment, however, failed to confer cross-tolerance to the hypothermic effect of hydralazine. These findings suggest that conditioning plays a predominant role in the tolerance produced by low but not by high treatment dosage. The data also suggest that conditioning might be a separate component in tolerance development, which is of special importance in tolerance to behavioral effects in the whole animal rather than to cellular or molecular effects.

Animals↗
PubMed1987

Effect of raphe lesions on the development of chronic tolerance to pentobarbital and cross-tolerance to ethanol.

Sham and electrolytic lesions of the dorsal, median, and median + dorsal raphe nuclei were made in different groups of rats, and the differential patterns of regional 5-HT depletion were verified chemically. One week later, an initial dose-response curve for the motor impairment effect (moving belt test) of pentobarbital was obtained. Matched subgroups of the animals in each lesioned group received daily gavage with either pentobarbital (50 mg/kg) or water for 36 days. Tolerance to the motor impairment effect of pentobarbital was measured at 4-day intervals. Lesions of the dorsal raphe nucleus had no influence on the development of tolerance, whereas median and median + dorsal raphe lesions resulted in slower development of tolerance, though plasma pentobarbital levels were unaltered. The effect of the combined lesion was similar to that of the median raphe lesion alone. A separate study revealed a similar differential effect of median versus dorsal raphe lesions on the development of cross-tolerance to ethanol.

Animals↗