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Z Amit

Publications and source records attributed to Z Amit.

At least 109 records · Page 6Linked to original sources

Aversive stimulus properties of morphine: evaluation using the drug preexposure conditioned taste aversion paradigm.

Interpretation of the finding that positive-reinforcing drugs such as morphine also possess possible aversive properties, as revealed by their ability to induce a conditioned taste aversion (CTA), remains problematic. This issue was addressed in the present study using the drug preexposure CTA paradigm. Water-deprived rats were given noncontingent preexposure to one of three doses of morphine (2.5, 5.0, or 15.0 mg/kg) or drug vehicle. Subsequently, animals in each of these preexposure groups were presented with a novel 0.1% saccharin-flavored solution followed immediately by injection with one of the same three morphine doses or drug vehicle. This procedure was repeated at 5-day intervals until six saccharin presentations had been performed. Results indicated that while the three morphine doses were differentially potent as taste aversion-conditioning agents, they were equipotent as preexposure agents serving to disrupt CTA. These data suggest that preexposure to morphine's predominantly positive-reinforcing (and non-CTA-inducing) properties is sufficient for preexposure disruption of subsequent morphine CTA. A second experiment indicated that the minimal effective preexposure dose is between 0.3 and 1.25 mg/kg of morphine. It is suggested that an important commonality may exist between the discriminative stimulus properties of morphine as a CTA-inducing agent and as a positive reinforcer.

Animals↗

Further evaluation of morphine aversion: maintenance of a taste aversion using a low, nonaversive morphine dose.

Previously, in an investigation of morphine-conditioned taste aversion (CTA), we found that limited preexposure to a low, nonaversive (non-CTA-inducing) dose of morphine (2.5 mg/kg) was as effective as preexposure to a higher, CTA-inducing dose (15 mg/kg) in blocking the formation of a subsequent morphine CTA. In the present study, we examined the capacity of this low, 2.5-mg/kg morphine dose to maintain a CTA initially induced by the 15-mg/kg dose. A standard CTA procedure was used. Results indicated that rats given three initial taste-drug pairings with 15 mg/kg morphine followed on subsequent pairing days by treatment with the low, non-CTA-inducing, 2.5-mg/kg dose continued to exhibit a strong CTA over 8 pairing days. A similar pattern was observed for animals continuing to receive taste-drug pairings with the 15-mg/kg dose. Animals receiving only one taste-drug pairing with the 15-mg/kg dose, followed on subsequent pairing days by 2.5-mg/kg conditioning, failed to show such a pattern of CTA. An intermediate CTA pattern was seen with animals conditioned with 15, 10, 5, and repeated 2.5-mg/kg doses over consecutive pairing days. These data suggest that exposure to a low dose of morphine, with no apparent CTA-inducing properties, is sufficient to maintain a previously established morphine taste aversion. Potential implications for understanding the apparent discriminative complexity of morphine's motivational properties are discussed.

Animals↗

Attenuation of ethanol-induced conditioned taste aversion by naloxazone: behavioral evidence for an opiate receptor-mediated morphine-ethanol interaction.

When rats are presented with a novel saccharin solution and immediately injected with either morphine or ethanol, they subsequently develop a conditioned taste aversion (CTA) to the saccharin solution which reflects the aversive component of the conditioning drug. The present study provides evidence which suggests that both morphine-induced and ethanol-induced CTAs can be blocked by the specific high-affinity binding opiate antagonist, naloxazone.

Animals↗

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↗

Conditioned place preference: an evaluation of morphine's positive reinforcing properties.

The place-preference paradigm was evaluated as a measure of morphine's positive reinforcing properties. Previous place-preference studies obtained a morphine place preference of 26%-63%. In order to examine whether differences in procedure may account for this scatter, the present experiment investigated whether there is any difference in the absolute magnitude of preference when animals are conditioned on their non-preferred side of the box or when animals are randomly assigned to the side of conditioning. Furthermore, the number of conditioning days was extended with 3 intervening test days, and drug doses were doubled following each test day. The results showed no significant difference between conditioning animals on their non-preferred side or randomly assigning them to the side of conditioning. However, by extending the number of conditioning days, as well as by following the drug regimen used, the animals showed a greater magnitude of preference than that observed in previous studies. The implications of these findings for the usage of this paradigm as a measure of morphine's positive reinforcing properties are discussed.

Animals↗

Selective depletion of norepinephrine in brain by N-2-chloroethyl-N-ethyl-2-bromobenzylamine fails to alter the voluntary consumption of ethanol in rats.

The effects of the selective norepinephrine neurotoxin, DSP-4, on the maintenance of voluntary consumption of ethanol was tested in male Long-Evans rats. The drug, DSP-4, produced a 51% reduction in whole brain levels of NE without affecting the consumption of ethanol. These results, however, do not rule out a role for NE in mediating this behavior.

Alcohol Drinking↗

Zimeldine: a review of its effects on ethanol consumption.

This review evaluates the literature and describes an extensive series of experiments which examined the effects of zimeldine , its metabolite norzimeldine and other serotonin and norepinephrine reuptake inhibitors on voluntary ethanol consumption in rats. The results of these experiments indicate that drugs which specifically inhibit serotonin reuptake are capable of decreasing voluntary ethanol consumption. The behavioral mechanism through which these drugs exert their effects seems to be extinction of the primary reinforcing properties of alcohol. These effects seem to be partially attenuated both by drugs which modulate the norepinephrine system as well as by the serotonin postsynaptic receptor blocker methergoline. The data presented in this review are discussed in terms of the involvement of the serotonin and norepinephrine systems in the mechanism of action of these drugs. In addition, several alternative hypotheses concerning the nature of the phenomenon are offered. Finally, the implications of these data for the possible development of a treatment procedure for problem drinkers is discussed.

Alcohol Drinking↗

Symmetrical effect of pre-exposure between alcohol and morphine on conditioned taste aversion.

It has previously been reported that pre-exposure to a psychoactive drug can block the conditioned taste aversion associated with that drug. This study was an attempt to investigate alcohol-morphine interactions using this pre-exposure paradigm. After two weeks of adaptation to a schedule of daily 30-minute access to water, rats were pre-exposed to morphine, ethanol, or the respective vehicle control every second day for three days before (Days 1, 3, 5) and after the first conditioning day (Days 8, 10, 12). On conditioning days (Days 7, 14), animals were first presented with a saccharin solution for 30 minutes following which animals that were pre-exposed to morphine were injected with ethanol while those pre-exposed to ethanol were administered with morphine. Saccharin was again presented on three more occasions (Days 21, 28, 35) without drug injection. Using the percent change in saccharin consumed from the first presentation as a measure of aversion, it was found that pre-exposure to morphine blocked ethanol conditioned taste aversion. Similarly, animals pre-exposed to ethanol showed less aversion to the saccharin paired with morphine. This is the first demonstration of a symmetrical relationship between alcohol and the opiates.

Animals↗

Isolation versus grouped housing in rats: differential effects of low doses of heroin in the place preference paradigm.

Male Long Evans rats were reared from weaning (21-23 days) either in isolation or in groups of four for 40 days. Animals were then individually introduced to a testing apparatus consisting of two distinct chambers. A modified place preference paradigm was used consisting of 3 phases: (1) An habituation phase (4 days) during which rats were allowed free access to the entire test apparatus for 15 min. periods daily; (2) A conditioning phase (4 days) during which rats were confined to their non-preferred side for 15 minutes each day immediately following subcutaneous injection of 0, 20, 40 and 80 micrograms/kg of heroin HCl; (3) A test phase (1 day) during which rats were again allowed free access to the testing chamber following injection of vehicle. The difference in time spent on the conditioned side during habituation and test periods was determined. The group-reared rats showed similar effects for all doses of heroin whereas the same magnitude of drug effect was attained only at the highest dose used in the isolated rats. This differential sensitivity to heroin in the place preference paradigm is discussed in terms of the modification of behavioral effects of opiates by environmental influences.

Animals↗

Cognitive inhibition of human gastric acid output--studies using telemetric measurements.

In study I subjects had two sessions--one to examine the effects of reading and another to study the effects of relaxation exercises. An incomplete crossover design was used. Subjects (N = 13) decreased mean acid output by 32.2% while reading and 2.5% after relaxation exercises (N = 14). In study II, six subjects each had one session to examine the effects on acid output of a difficult maze-solving task. Mean acid output during maze-solving decreased 52.6% relative to the control period. The results of these two studies suggest that the degree of cognitive involvement is an important factor in the decrease of acid output. A modification of the Heidelberg telemetry equipment was described. It permitted a continuous measure of gastric acid output, was relatively nonaversive to subjects, and minimized the risk of cephalic or gastric phase effects of acid secretion due to the measuring technique. It is recommended as a valuable adjunct for studies designed to change gastric acidity.

Adolescent↗

Effects of heat-stress on behavior and the pituitary adrenal axis in rats.

Three experiments were performed in order to analyse the behavioral and biochemical correlates of four different intensities of the same stressor. In Experiment 1, rats were exposed to heat stress (hot-plate) of varying temperatures for 30 seconds. Activity was recorded in an open field immediately after stress for 30 minutes. The data revealed that the milder temperatures increased (21, 47, 52 degrees C), while the higher temperature (57 degrees C) decreased activity. Experiment 2 assessed the pituitary-adrenal response to the different temperatures by measuring levels of plasma corticosterone 30 minutes after stress. The four levels of hot-plate temperatures induced differential levels of corticosterone which may best be described as an inverted U-shaped function, with only the extreme temperature (57 degrees) inducing a significant elevation in levels of the steroid. Experiment 3 further manipulated the pituitary adrenal axis by administering dexamethasone 25 hr and 1 hr before stress and ACTH 15 min before stress. Both affected activity levels by depressing locomotion regardless of the stress intensity. These results are compared to other studies that have addressed the question of stress-induced activation and it is suggested that stress is not a unitary concept, but interacts with the performance of certain behaviors to produce both facilatory or inhibitory results.

Adrenocorticotropic Hormone↗

Stress induced suppression of maintenance but not of acquisition of ethanol consumption in rats.

Male Wistar rats were given a free-choice between water and increasing concentrations of ethanol from 3% to 11% (v/v) during the acquisition phase. Thereafter, animals were maintained on a choice between water and 11% ethanol for the balance of the experiment. For 5 days prior to and for periods during the acquisition and maintenance phases, the animals were exposed to electric footshock, restraint or no stress. The results showed no differences in ethanol drinking patterns among the groups during the acquisition phase. However, in the maintenance phase, both footshock and restraint suppressed the increase in ethanol intake seen in the no-stress control group.

Alcohol Drinking↗

Alcohol-induced euphoria enhanced by disulfiram and calcium carbimide.

In a double-blind study, subjects were treated with either disulfiram or calcium carbimide, inhibitors of acetaldehyde elimination, prior to consumption of low doses of alcohol. Self-rating scales, individual interviews, and observations by independent judges revealed that experimental subjects manifested enhanced changes in mood and euphoria compared to placebo control subjects.

Acetaldehyde↗

Effects of chronic naltrexone on amphetamine locomotor activity.

Animals from two different populations of Wistar rats were chronically pretreated with naltrexone for 8 days. After a 2-day rest period, animals were tested with amphetamine for locomotor activity in the open-field with or without white noise (Day 2). The rats were similarly retested on Day 7 and Day 14. New colony animals showed a significant attenuation in amphetamine locomotor activity in the absence of noise only. In contrast, chronic naltrexone significantly decreased amphetamine activity in old colony animals only under noise conditions. The possibility of an inhibitory role opiate receptors on the dopamine neuro-transmission is discussed.

Amphetamine↗

Intraventricular self-administration of leucine-enkephalin by laboratory rats.

Naive laboratory rats, without pre-exposure to operant training procedures or to opioids, were shown to self-administer directly into their cerebral ventricles the endogenous opiate peptide, leucine-enkephalin. They were shown to self-administer the peptide consistently for six consecutive days with no indication of the development of tolerance. The results indicate that leucine-enkephalin may possess potent reinforcing properties and suggests that it may play a role as an endogenous reward transmitter.

Animals↗

An investigation of the mechanisms of action of 5-hydroxytryptamine in the suppression of ethanol intake.

The effect of blockage of 5-hydroxytryptamine and norepinephrine uptake on voluntary ethanol consumption in rats was investigated. It was demonstrated that attenuation of ethanol intake occurred only as a result of treatment with specific 5-hydroxytryptamine uptake inhibitors. These results suggested that increasing the availability of central 5-hydroxytryptamine may in some way interfere with the positive reinforcing properties of ethanol. The second phase was designed to determine whether the attenuation of ethanol intake following blockade of 5-hydroxytryptamine uptake may be due to increased post-synaptic activity. Ethanol-preferring animals were pretreated with methergoline, a post-synaptic receptor blocker, followed by treatment with zimelidine, a 5-hydroxytryptamine uptake inhibitor. The results indicate that treatment with methergoline did not alter the zimelidine-induced attenuation of ethanol intake. Based on these results it is suggested that blockade of 5-hydroxytryptamine uptake produces an attenuation of ethanol intake but not as a result of increased post-synaptic activity.

Alcohol Drinking↗