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Z Amit

Publications and source records attributed to Z Amit.

At least 91 records · Page 5Linked to original sources
PubMed1987

The role of acetaldehyde-metabolizing enzymes in the mediation of ethanol consumption: an investigation using a simulated drinking bout.

Laboratory rats in a 24 hr free choice paradigm consume ethanol in a series of discrete drinking bouts. However, little research has been directed at establishing whether these individual bouts were pharmacologically relevant to animals. The present study was designed to investigate the pharmacological efficacy of a simulated ethanol drinking bout and the possible role of acetaldehyde (ACH) and its metabolizing enzymes in mediating these effects using various enzyme manipulations. Following an ethanol screening procedure (2% to 10%, free choice) to establish a drinking baseline, animals were deprived of ethanol for a two week period. Using a limited access procedure, animals were then presented with a 10% ethanol solution for a 10 min period each day for 10 days. On Days 11-15, 4 hr prior to ethanol presentation, animals were divided into four groups and received i.p. injections of either saline (S), 4-methylpyrazole (4MP), cyanamide (C) or 4-methylpyrazole + cyanamide (4MP + C). This latter treatment condition has been shown to prevent the accumulation of ACH in the periphery by cyanamide. On Day 12, 10 min after the drinking session, animals were placed in open field chambers and locomotor activity was recorded for 5 min. Results indicated that animals pretreated with cyanamide (groups S + C and 4MP + C) consumed significantly more ethanol across the 5 test days than groups S + S and 4MP + S. Locomotor activity was significantly depressed for animals pretreated with cyanamide alone (C + S), although drinking levels were comparable to all other groups on Day 12. Together, these data demonstrate that a stimulated drinking bout is a pharmacologically meaningful event since it can be altered by manipulating acetaldehyde-metabolizing enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
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↗
PubMed1986

Effects of pimozide on appetitive behavior and locomotor activity: dissimilarity of effects when compared to extinction.

The effects of pimozide were examined in a runway paradigm using food reward. Rats received one of three doses of pimozide, vehicle or Ringer's prior to testing. Two additional groups received pimozide or vehicle after the test trial in the home cage. An extinction group received no food in the goal box on test days. Several components of running behavior were assessed as was food consumed in the goal box. Effects of pimozide on general locomotor activity were assessed in the open-field following the runway phase. Results of the runway indicated that pimozide-treated rats differed from the extinction group in latencies to leave the start box and enter the goal box. Pimozide-treated rats consumed less saccharin-flavored food than controls. The post-treatment pimozide group showed a reduction in saccharin-food intake suggesting a conditioned taste aversion. Thus, the reduction observed in the pretreated pimozide group may be due to some unconditioned aversion induced by the drug. Open-field revealed that pimozide resulted in lower activity than controls. This study indicates that the effects of pimozide on food reinforcement are not similar to the effects seen in extinction. These data are consistent with the hypothesis that the effects of pimozide, in this paradigm, constitute an interference with motor responses as opposed to an attenuation of reward properties of the stimuli.

Animals↗
PubMed1986

The effects of pimozide on drinking behavior in the rat: an investigation using the conditioned taste aversion paradigm.

In an attempt to examine the potential aversive properties of the neuroleptic pimozide, a conventional conditioned taste aversion (CTA) paradigm was employed. Rats were either pretreated with pimozide (1.0 mg/kg) before the presentation of a familiar or novel saccharin-flavored solution or tap water or received injections of pimozide after the presentation of a novel saccharin solution. Following this procedure, rats were given a two bottle choice test under drug-free conditions. All pretreated pimozide groups demonstrated a significant unconditioned reduction in fluid intake relative to the vehicle control group. These pimozide groups having different drinking histories did not differ from one another. Although pimozide did not induce a CTA in rats post-treated with this neuroleptic, overall this group drank significantly less saccharin than the control group. Furthermore, on the two bottle choice test, rats which received contingent exposure to pimozide and saccharin (pre and post conditions), did not demonstrate a preference for the saccharin solution. These results suggest that the reduction in fluid intake observed in the pretreated pimozide groups may be due to some unconditioned aversive state induced by the drug. These data indicate that the mechanisms involved in the reduction of fluid intake induced by pimozide may be unrelated to a manipulation of the reinforcing properties of the appetitive stimulus.

Analysis of Variance↗
PubMed1986

Differential effects of isolation housing on the conditioned place preference produced by cocaine and amphetamine.

Rats were obtained at 21 days of age and were housed either in isolation or in groups of 4 for 6 weeks. They were then tested for their sensitivity to cocaine HCl (0.31, 0.62, 1.25 or 2.5 mg/kg) or d-amphetamine SO4 (0.031, 0.062, 0.125, 0.25 or 0.5 mg/kg) using a modified place preference paradigm. The isolated rats were insensitive to cocaine in this paradigm whereas the group-housed animals showed peak effects at the lowest dose of this drug. In contrast, there was no difference in sensitivity to amphetamine as a function of housing conditions. These data strengthen the notion that the effects of the early environment on drug sensitivity in the adult are specific to certain classes of drugs. Further, these data lend support to the notion that the effects of cocaine and amphetamine in the place preference paradigm are mediated by different neural systems.

Amphetamine↗
PubMed1986

Conditioned taste aversion to ethanol induced by zimeldine.

Conditioned taste aversions (CTA) were induced to both ethanol and saccharin solutions with the serotonin uptake inhibitor Zimeldine. When animals were pretreated with Zimeldine prior to the presentation of a novel flavour a CTA did not result. However, there is evidence that Zimeldine induces an unconditioned suppression of drinking. These results are discussed in terms of their relevance to Zimeldine's effects on voluntary ethanol consumption.

5-Hydroxytryptophan↗
PubMed1986

Voluntary ethanol consumption in rats: an examination of blood/brain ethanol levels and behavior.

The temporal pattern of food, water, and ethanol consumption was examined in rats maintained on a 24-hr ethanol access schedule. These data demonstrated that rats consume ethanol in discrete, short bouts mainly during the lights-out cycle. Simulation of a single ethanol drinking bout was carried out by limiting ethanol access to a short time period each day. Detectable levels of blood and brain ethanol were observed following these individual drinking bouts. Behavioral evidence is provided indicating that rats drink ethanol in quantities sufficient to produce pharmacological effects.

Alcohol Drinking↗
PubMed1986

Stress-induced analgesia: adaptive pain suppression.

In this paper we have examined the phenomenon of stress-induced analgesia. We have described the procedures used to measure analgesia and have suggested that the tests can be designed not only to indicate changes in pain threshold but also to allow for the determination of the capacity to execute adaptive behavior. Aside from enabling the analysis of responses, tests that induce reflexive as well as nonreflexive behavior may have the capacity to separate the more complex aspects of pain such as the possible presence of two components of pain, sensory/discriminative and motivational/affective. These components may be of fundamental importance for any attempt to understand the biological significance of SIA. Our examination of the neurotransmitter and neuropeptide systems has revealed that they are affected by the same manipulations that induce SIA. These amines and perhaps peptides play an integral role in learning, motivation, and performance. We conclude that the functional advantage of a reduction of pain during stressful situations is significant because it allows the animal to react in threatening and perhaps critical situations as if there were no pain. Once the pain system is inhibited, other systems modulate and mediate adaptive responses that expedite the survival of the animal.

Analgesia↗
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

Acetaldehyde and morphine interaction in the preexposure conditioned taste aversion paradigm in the rat.

The interaction between acetaldehyde, the primary metabolite of ethanol, and morphine was examined in the preexposure conditioned taste aversion (CTA) paradigm. Rats that were preexposed to acetaldehyde did not display a CTA to morphine. While acetaldehyde at the dose tested did not induce a strong CTA, morphine preexposure, however, reversed the decrease in saccharin associated with acetaldehyde injection thus reflecting a symmetrical interaction between acetaldehyde and morphine. Implications for a mechanism of ethanol-opiates interaction are discussed.

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↗
PubMed1985

Involvement of dopamine in the aversive stimulus properties of cocaine in rats.

Previous studies of cocaine self-administration have demonstrated central dopaminergic involvement in cocaine's positive reinforcing properties. The present study reports the ability of pimozide, a dopamine receptor antagonist, to attenuate a conditioned taste aversion induced by repeated injections of cocaine. Rats placed on a daily water deprivation schedule were subsequently presented with a novel saccharin taste in their drinking fluid immediately followed by administration of four 9 mg/kg injections of cocaine spaced at 20 min intervals. These animals exhibited a reduction in saccharin intake on subsequent presentations. Animals pretreated with pimozide 90 min prior to the saccharin-cocaine pairings failed to show this reduction. In a second experiment using an identical procedure, repeated injections of lithium chloride were shown to induce a CTA both in pimozide-pretreated and control animals. The results of these two experiments are consistent with the notion that a functional relationship may exist between neurochemical mechanisms underlying both the aversive (CTA-inducing) and positive reinforcing properties of self-administered drugs such as cocaine.

Animals↗
PubMed1985

An examination of heroin conditioning in preferred and nonpreferred environments and in differentially housed mature and immature rats.

The study addressed two issues. First, we examined the effectiveness of heroin as a conditioning agent in a preferred environment using a place preference paradigm. Four daily injections of 80 micrograms/kg (SC) of heroin HCl were paired with environments that rats initially found to be either preferred or non-preferred. In subsequent tests, only those that had experienced the drug effects in the non-preferred environment increased the percentage of time spent in that environment. Rats conditioned in the test chamber that was initially preferred failed to increase the amount of time spent in that chamber post-conditioning. These results suggest that the conditioned place preference paradigm does not simply assess the rewarding consequence of heroin injections. We also examined the effects of grouped and isolation housing conditions on the heroin-produced conditioned place preference. Rats were housed under these conditions either immediately post weaning or at 120 days of age. There was a difference between the magnitude of the place preference produced by 20 micrograms/kg heroin in the isolated but not in the group housed rats. When isolated at weaning the rats were less sensitive to the drug than were rats isolated at maturity. These data are discussed with particular reference to the development of the endogenous opioid system.

Aging↗
PubMed1985

Receptor stereospecificity in opiate-ethanol interaction using the preexposure-conditioned taste aversion (CTA) paradigm.

In the first experiment, rats were conditioned with different doses of levorphanol or dextrorphan to a novel tasting saccharin solution. In the second experiment, rats were either preexposed to levorphanol or dextrorphan and conditioned with either morphine or ethanol to the saccharin solution. The results showed that levorphanol, but not dextrorphan, at 1, 5 and 10 mg/kg doses effectively induced a CTA. Preexposure to the 5 mg/kg dose of levorphanol blocked both morphine- and ethanol-induced CTAs. Dextrorphan at the same dose did not affect the CTAs. These findings are discussed in terms of the involvement of the opiate receptors in opiate-ethanol interaction.

Animals↗
PubMed1985

Interactions between ACTH, morphine, and naloxone and their effects on locomotor behavior.

A series of behavioral experiments were performed to evaluate possible interactions between ACTH, morphine and naloxone with regard to locomotor activity in an open field. Manipulations included the administration of one of the drugs followed 30 min later by one of the other drugs. This allowed the examination of the effects of a drug on the ongoing behavior induced by the other drug. In two other experiments which differed in the time of day they were run, locomotor patterns as the result of the administration of combinations of the three drugs were examined for three hours. The results of the present experiments suggest a possible common mode of action of ACTH, opiate agonists and antagonists that was dependent on time of day and stress intensity.

Adrenocorticotropic Hormone↗
PubMed1985

The role of gamma-aminobutyric acid (GABA) in the regulation of ethanol and acetaldehyde self-administration.

Laboratory rats were presented with ethanol and water in a free-choice paradigm to determine each animal's preference for ethanol. Following a three week ethanol free period, it was observed that the duration of gamma-butyrolactone induced loss of righting reflex was negatively correlated to voluntary ethanol intake. It was also observed that the rate of intracerebroventricular self-administration of acetaldehyde was positively correlated with the latency to gamma-butyrolactone induced loss of righting reflex. These findings indicate that high ethanol drinking rats and high acetaldehyde self-administrating rats are less sensitive to the sedative action of gamma-butyrolactone.

4-Butyrolactone↗