Alcohol preference in the laboratory rat induced by hypothalamic stimulation.
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Alcohol Drinking↗
Biomedical subjects
Z Amit
Publications and source records attributed to Z Amit.
Comment on the increased resistance-to-extinction of an avoidance response induced by certain drugs.
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Animals↗
Conditioned taste aversions produced by active and inactive cannabinoids.
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Animals↗
ACTH1-39 but not naltrexone produces biphasic effects on locomotor activity.
Two experiments were conducted in order to investigate the effects of chronic ACTH and naltrexone treatment on motor activity in an open-field. In the first experiment, Wistar rats received two daily injections of either ACTH1-39-saline, naltrexone-saline, ACTH1-39-naltrexone or saline-saline for 24 consecutive days. Immediately following injections, motor activity was measured every fourth day. The results indicated that ACTH and naltrexone each had depressive effects on motor activity that did not dissipate over 24 days. In the second experiment, the procedure was similar to the first except that motor activity was measured at five hours postinjection. The results revealed that naltrexone by itself or in combination with ACTH had no observable effect on motor activity. ACTH was observed to have a stimulatory effect on motor activity that decreased over days and was not naltrexone reversible. The results are discussed in terms of different mechanisms underlying the effects of ACTH and naltrexone.
Adrenocorticotropic Hormone↗
Behavioral support for an ACTH receptor in the CNS.
In this report we present a series of experiments which have led us to support the notion of the presence of an ACTH receptor in the CNS. A short intense heat-stress (hot-plate) applied to the paws of rats will temporarily reduce activity. During the course of experimentation we were able to eliminate a number of logical mediators. Neither adrenalectomy, adrenal-medullectomy, naloxone administration, nor alpha-MSH-(1-12) were able to affect the observed akinesia. Hypophysectomy, however, was able to abolish or mask the behavior and the reduction in activity could be reinstated by the administration of ACTH-(4-10) to hypophysectomised rats. These data support the notion that a short intense stressor can release ACTH and that this ACTH can be responsible for mediating the short term reduction in activity. In addition, the fact that ACTH-(4-10) has only minimal steroidogenic properties and was able to reinstate the behavior led us to speculate that these effects were of central origin. Furthermore, since naloxone was not capable of altering the behavior, the suggestion is that ACTH in this paradigm acted at a receptor site apart from the naloxone sensitive receptor. This site may in fact be an ACTH specific receptor.
Adrenal Medulla↗
Possible involvement of acetaldehyde, norepinephrine and their tetrahydroisoquinoline derivatives in the regulation of ethanol seld-administration.
In this study, we examined the possible role of acetaldehyde in the mediation of the reinforcing properties of ethanol. We also examined the possible interaction of acetaldehyde and brain norepinephrine in this mediation. We found that rats will self-administer acetaldehyde delivered into the cerebral ventricles, and that this operant behaviour can be attenuated by injections of a dopamine-beta-hydroxylase inhibitor. The results are discussed in terms of a role for tetrahydroisoquinoline alkaloids in alcoholism.
Acetaldehyde↗
Conditioned place preference induced by intraventricular infusions of acetaldehyde.
Multiple intracerebroventricular infusions of acetaldehyde were shown to induce conditioned place preference in laboratory rats. Those animals receiving acetaldehyde infusions displayed an increased preference for environmental cues previously paired with the drug administration. These results indicate that acetaldehyde, when present in the brain, may have reinforcing properties.
Acetaldehyde↗
Stereospecific interaction between alcohol and opiates mediated by the mu high-affinity binding receptor.
Experiment 1 revealed that preexposure to morphine blocked ethanol-induced CTA, and that conversely, preexposure to ethanol blocked morphine-induced CTA. In experiment 2, naloxazone injected 4.5 hr before the preexposure drug significantly reversed the interaction between morphine and ethanol. The results of Experiment 3 showed that preexposure to levorphanol blocked both morphine- and ethanol-induced CTAs while dextrorphan at the same dose did not affect the CTAs. These findings are discussed in terms of the involvement of the opiate receptors and their ligands in opiate-ethanol interaction.
Animals↗
Norepinephrine turnover and voluntary consumption of ethanol in the rat.
The effect of a centrally acting noradrenergic agonist on voluntary ethanol intake was investigated in the laboratory rat. Doses of 1.5, 7.5, 15 and 25 mg/kg of FLA-136 were administered to animals chronically exposed to ethanol on a free choice basis. Administration of the highest dose of the drug brought about a 40% reduction in voluntary ethanol intake with no significant effect on total fluid consumption. These results would seem to indicate a possible functional relationship between rate of norepinephrine turnover and amounts of ethanol voluntarily consumed by the laboratory rat.
Alcohol Drinking↗
The effects of zimeldine on voluntary ethanol consumption: studies on the mechanism of action.
Research from our laboratory has shown that several specific serotonin uptake blockers (zimeldine, fluoxetine, sertraline) are effective in reducing voluntary ethanol consumption in rats. However, the mechanism of action of these drugs is not well understood. The series of experiments presented here examined whether zimeldine produces its effects on ethanol consumption via a serotonin mediated anorexic action. In addition the effects of chronic administration of zimeldine were examined in rats drinking a dextrose solution, as well as in ethanol-consuming animals following 5-HT depletion with p-chloroamphetamine. The results indicate that zimeldine reduces the consumption of ethanol, dextrose and saccharin solutions. However, these effects on fluid consumption are not blocked by prior serotonin depletion. The results are discussed in terms of serotonin's role in this process in general and the possibility that zimeldine's effects are not directly related to its capacity to block the reuptake of serotonin.
Alcohol Drinking↗
A correlation between voluntary ethanol consumption and brain catalase activity in the rat.
The relationship between voluntary ethanol consumption and brain catalase activity was investigated in male Long Evans rats. In the first study, rats which were voluntarily consuming alcohol or water for 25 days were sacrificed by decapitation immediately (group A) or 15 days (group B) following withdrawal of alcohol and their brains analysed for catalase activity. Mean brain catalase activity did not differ among the two groups of rats exposed to ethanol and the ones exposed to water only. Furthermore, there were significant positive correlations between individual voluntary ethanol intake and catalase activity in both groups, (group A:r = .69, p less than or equal to 0.05; group B:r = .54, p less than or equal to 0.05). In the second study, rats were forced to drink high levels of ethanol presented as the only source of fluid for 25 days. Rats were sacrificed and brain, liver, muscle and heart tissue were extracted and analysed for catalase activity. There were no differences in mean brain catalase activity between water and forced ethanol drinking rats indicating that the enzyme was not inducible by high volume ethanol consumption. The results suggest that inherent differences in brain catalase activity may be one of the factors in determining an animal's propensity to voluntarily consume ethanol.
Acetaldehyde↗
A two dimensional model of alcohol consumption: possible interaction of brain catalase and aldehyde dehydrogenase.
The possible existence of a biological marker system mediating voluntary consumption of ethanol in rats has been examined in a series of studies. The working hypothesis underlying this research was that acetaldehyde, the primary metabolite of ethanol, mediates the positive reinforcing properties of ethanol and thus underlies the voluntary consumption of ethanol in both animals and humans. We further hypothesized that brain catalase and aldehyde dehydrogenase, the enzymes controlling the production and elimination of acetaldehyde in the brain, may represent a biological marker system underlying the affinity of the animals to consume ethanol. Data demonstrating that the activity levels of these enzymes are positively correlated with alcohol ingestion seems to suggest that it is likely that the enzyme activity can serve as a predictor of the propensity to drink alcohol. A predictive model is proposed which describes the modulation of voluntary ethanol intake through the activity of these enzymes and their role in determining rates of formation and degradation of acetaldehyde in the brain.
Acetaldehyde↗
Brain ALDH as a possible modulator of voluntary ethanol intake.
The relationship between voluntary ethanol intake and brain aldehyde dehydrogenase (ALDH) activity was investigated in the laboratory rat. Voluntary ethanol intake was compared to subcellular forms of brain ALDH. Mitochondrial, microsomal and cytosolic fractions were prepared and recovered ALDH activity of each form was compared to voluntary ethanol intake in Long Evans rats. Strong correlations were found between both mitochondrial and microsomal ALDH fractions and ethanol intake. No activity was observed in cytosolic fraction as measured with aromatic or aliphatic aldehydes. In addition, microsomal activity was detected with aromatic aldehydes only, whereas the mitochondrial form would oxidize both aromatic and aliphatic aldehydes.
Acetaldehyde↗
A multi-dimensional examination of the positive reinforcing properties of acetaldehyde.
The suggestion that acetaldehyde may be endowed with positive reinforcing properties and may in fact mediate some of the psychopharmacological actions of ethanol has been examined by us and other investigators using a variety of paradigms. We first reported that non-dependent animals would self-administer acetaldehyde through an intra-cerebroventricular route. In addition, we have demonstrated that central infusion induced a conditioned place preference. We have also shown that an animal's propensity to self-administer acetaldehyde directly into the brain was related to its subsequent voluntary intake of ethanol. Lastly, we have reported that inhibition of acetaldehyde metabolism resulted in an enhancement of alcohol-induced euphoria in man. The data collected to date from four different paradigms strongly support the notion that acetaldehyde is endowed with positive reinforcing properties which may play a critical role in the mediation of ethanol euphoria.
Acetaldehyde↗
Treatment with sertraline, a new serotonin uptake inhibitor, reduces voluntary ethanol consumption in rats.
Serotonin uptake blockers have been shown to produce a robust and reliable reduction in voluntary ethanol consumption in rats. These compounds are currently under investigation as potential treatments for alcohol abuse in humans. It is uncertain whether serotonin uptake blockers exert their effects directly through serotonergic mechanisms or whether an interaction between the serotonin and noradrenergic systems is involved. The present series of experiments was designed to examine the effects of sertraline, a new selective serotonin uptake blocker, on voluntary ethanol intake. Sertraline produced a robust reduction in voluntary ethanol intake. It appears therefore, that increasing selectivity for serotonin blockade does not alter the efficacy of these compounds as antialcohol agents. The drug also reduced the consumption of a saccharin solution indicating that sertraline's effects are not specific to ethanol intake.
1-Naphthylamine↗
A further examination of the effects of sertraline on voluntary ethanol consumption.
Previous work with the serotonin uptake blocker, sertraline, demonstrated that the drug suppressed the consumption of ethanol and saccharin as well as body weight gain. There is increasing evidence that many serotonergic agents such as agonists, releasing agents and uptake blockers, reduce food intake. Sertraline was found to have a robust anorexic action. In this paper evidence is presented which supports the hypothesis that the administration of serotonin uptake blockers reduce ethanol consumption as a secondary consequence of a suppression in food intake.
1-Naphthylamine↗
Age-dependent effects of isolation housing on the self-administration of ethanol in laboratory rats.
Studies of the influence of housing conditions on ethanol self-administration have been inconsistent, with findings that isolation housing increases, decreases or produces no effects on ethanol intake. One possible explanation for these discrepant findings is that the effects of housing are dependent on the age at which the manipulation is performed. In the present experiment rats were housed from weaning or from age 65 days in either an isolated or grouped condition. After 12 weeks, they were tested for the voluntary oral self-administration of ethanol. Although all rats consumed comparable quantities of ethanol when lower concentrations were available, the rats isolated from weaning consumed significantly greater amounts of more concentrated ethanol than their group-housed counterparts. In contrast, there was no difference in ethanol consumption between isolated and grouped rats when they were differentially housed at maturity. These data suggest that an important determinant of ethanol intake in rats is related to environmental factors and that the influence of these factors is age-dependent.
Aging↗
Attenuation of voluntary ethanol consumption by dopamine-beta-hydroxylase inhibition (FLA-57): mediated by changes in aversion, reinforcement or both.
The dopamine-beta-hydroxylase inhibitor, FLA-57, was reported by several investigators to reduce voluntary ethanol consumption in rats. The nature of the effect of FLA-57 on this behavior had been attributed to its involvement in both the mediation of positive reinforcing and aversive processes. In the present study, the capacity of FLA-57 to induce a conditioned taste aversion (CTA) in both a forward and a "nominally backward conditioning" paradigms was investigated. This was done in an attempt to assess the possible contribution of a FLA-57-induced CTA to the previously observed reduction in ethanol intake in several drinking studies. Furthermore, the ability of FLA-57 to induce a CTA in a nonnovel situation, where the taste of the presented solution (ethanol or saccharin) was familiar to the animals, was also assessed. The inclusion of these specific conditions was necessitated by the attempt to create conditions similar to those prevalent in drinking studies. We found that FLA-57, in both conditioning paradigms, induced a significant CTA. Animals, naive and experienced with the taste of ethanol or saccharin, exhibited a CTA following the administration of FLA-57. However, the magnitude and rate of extinction of the observed CTAs did not resemble those observed in studies on the effects of FLA-57 on ethanol intake. The results of this study suggest that while it is possible that FLA-57 exerts its effect on ethanol intake, at least in part, through an aversive mechanism, such a mechanism is unlikely to be the exclusive process through which ethanol ingestion is attenuated.
Alcohol Deterrents↗