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Biomedical subjects

H L Altshuler

Publications and source records attributed to H L Altshuler.

At least 19 recordsLinked to original sources
PubMed1988

Neonatal and maternal hair zinc levels in a nonhuman primate model of the fetal alcohol syndrome.

The role of zinc deficiency in the etiology of ethanol-associated fetotoxicity was assessed by measurement of maternal and newborn hair zinc content in a nonhuman primate model of the fetal alcohol syndrome. The model best approximates the human situation for length of gestation and type of placentation, coupled with the ability to control for nutritional factors. All mothers received 110% of their minimum daily caloric requirements as a balanced, nutritionally complete diet, including a minimum of 3.5 mg zinc per day. Over a 2-year period, maternal hair samples from 17 pregnancies (using 12 females) were obtained at term. There were 16 live, full-term neonates (nine ethanol exposed and seven control) from whom samples were taken within 1 hr of birth. The ethanol-exposed infant monkeys had a significantly higher incidence of craniofacial dysmorphology and developmental delay compared to the controls. There was no difference in hair zinc levels between ethanol-exposed and control animals for either the mothers or the newborns. Neonatal levels were, however, consistently higher than corresponding maternal. Although the findings cannot exclude transient or early gestational zinc deficiency as a factor, they provide further evidence that ethanol (and/or its metabolites) is the proximate toxin in the type of fetal injury seen in the fetal alcohol syndrome.

Animals↗
PubMed1981

Animal models for alcohol research.

Many animal models have been used for alcoholism research. No single model is suitable for all types of research about alcohol, its actions and abuse. This article surveys the varieties of models that have been used and categorizes them into classes called "chronic", "reinforcement" and "genetic" models and discusses the strengths, weaknesses and applications of each group. The diversity and scope of alcoholism offers unique challenges to the conduct of laboratory research with experimental animals. Animal models (AM) of the disease would have to encompass a broad range of variables No single model can incorporate all aspects of the disorder nor fulfill the needs of all research projects. Consequently, many different AM have been proposed. This review classifies those models, describes their underlying premises, experimental applications and their relative strengths and limitations. The scientific literature contains numerous examples of essentially sound experiments that lack credibility because of weaknesses in design aspects associated with the selection or use of AM. The alcoholism literature cannot be excluded from that statement. There are many examples of the inappropriate use of AM in alcoholism research and of poorly conceived attempts to use models developed for specific experimental applications in experiments requiring an entirely different approach. Furthermore, a persistent problem that is unique to alcoholism research relates to providing appropriate controls. Since alcohol (ALC) has caloric as well as pharmacological effects, dual controls must be established. The caloric effects of ALC can alter an animal's nutritional state in important ways. Therefore, studies involving more than one or two ALC doses must provide adequate controls for both the pharmacological and the non-specific nutritive effects. Unfortunately, such controls are often difficult to establish and validate.

Alcoholism↗
PubMed1981

A subhuman primate model for fetal alcohol syndrome research.

The object of this project was to develop and evaluate new methods for the establishment of a subhuman primate model (SPM) of the fetal alcohol syndrome (FAS). Adult Rhesus monkeys (5.5--16.0 kg) were used as subjects. All were proven breeders and all matings in this project were repeats of matings that had previously produced normal offspring. The animals received alcohol (ALC) via permanently implanted intragastric cannulae (IGC) at doses to establish blood alcohol concentrations (BAC) within 2 selected ranges. Initially the high dose group received ALC doses designed to maintain BAC of approximately 150 mg/100 ml, and the other at 75--100 mg/100 ml. Daily ad lib food intake was monitored. The animals received infusions of liquid diet through the IGC so that their daily intake of balanced calories was 110% of the minimum daily requirements. The overall experimental design of this study called for each animal to have on ALC exposed pregnancy, serve as a pair-fed control for its own ALC exposed pregnancy and serve as a pair-fed control for a different animal. The preliminary results indicate that the IGC was suitable for use in pregnant rhesus monkeys. Two animals that were receiving ALC at doses and schedules to maintain the BAC above 150 mg/100 ml aborted during the first trimester of their pregnancies. No abortions have been observed in animals receiving either control diets or lower doses of ALC. In summary, this preliminary study demonstrates that it is feasible to use an IGC as a method for maintaining precise control over a pregnant Rhesus monkey's ALC exposure and nutritional status and thereby establish a SPM of FAS that meets critical control criteria.

Animals↗
PubMed1980

Time-dependent changes in the effects of cholinesterase inhibitors on shuttle-box avoidance.

Physostigmine and neostigmine were compared for their effects on shuttle-box avoidance acquisition and retention. Physostigmine impaired acquisition at doses lower than neostigmine. Avoidance performance 1, 7, or 14 days after acquisition was impaired by the administration of 0.4 mg/kg physostigmine or an equimolar dose of neostigmine. The effects of lower doses of physostigmine, but not of neostigmine, were dependent upon the time of original training relative to drug administration and retesting. The results suggest that the peripheral effects of higher doses of cholinesterase inhibitors impair avoidance performance. The effects of lower doses of physostigmine on acquisition and the time-dependent effects on subsequent performance are probably due to the central actions of this drug.

Animals↗
PubMed1980

Changes in the rhesus monkey's EEG responses to ethanol during chronic exposure.

This study was designated to document the changes in the CNS response to ethanol during chronic exposure in 5 male, 3.5--5.0 kg rhesus monkeys. Electrodes were implanted bilaterally into the amygdala, hippocampus and the calvarium over the frontal and temporal cortex. Ethanol or control solutions were administered intragastrically through indwelling cannulae. The 1.25 g/kg ethanol challenge dose was administered during EEG recordings. After one challenge dose, the animals received 60 days of chronic alcohol exposure (3.0 g/kg/day increasing to 8.0 g/kg/day). EEG was recorded every 10 days and analyzed by period analysis. Changes in the effect of the challenge dose were assessed by determining the percentage change of the EEG from pre-dose levels to selected times post-dose throughout the chronic alcohol exposure. The EEG response changed significantly during chronic alcohol treatment. Although each structure exhibited a slightly different pattern of change, the overall change was a shift from an excitatory response in the non-tolerant animal to an EEG slowing during chronic exposure. We suggest that such a change may be useful as a diagnostic marker for alcohol tolerance. In addition, the differential nature of the in vivo expression of alcohol tolerance in each brain area suggests that such analysis may provide a valuable tool for understanding the mechanism and expression of alcohol tolerance in the CNS.

Alcoholism↗
PubMed1979

Altered response to apomorphine and haloperidol after nine days of cocaine injections.

Sprague Dawley rats, pretreated with nine daily injections of 20 mg/Kg cocaine or saline, were evaluated for aspects of their behavioral response to apomorphine, haloperidol, or cocaine, twenty-four hours after their last pretreatment injection. Data obtained from saline and cocaine pretreated animals indicated that: cocaine pretreated rats were more sensitive to haloperidol-induced catalepsy, less responsive to some of the stereotypic effects of apomorphine and similar in their responses to the anticataleptic properties of cocaine.

Animals↗
PubMed1979

Effects of cocaine on sensory evoked potentials recorded from hypothalamus and limbic structures.

1. The present investigation was intended to examine the effects of the acute administration of several doses of cocaine on sensory evoked responses of freely moving rats. 2. Each structure and each component of the average sensory evoked potentials were affected by cocaine differently. 3. The changes induced by cocaine differ from those observed following other drug treatments. Therefore, it may be assumed that the changes observed are related directly to cocaine. 4. The present observation demonstrated a greater degree of sensitivity to low doses of cocaine than other types of electrophysiological recordings. In general cocaine in the lower doses (0.25 or 0.5 mg/kg) induced an increase in the sensory amplitude response while in the highest dose (10.0 mg/kg) attenuation of the sensory responses was obtained. 5. We assume that the euphoric effect induced by cocaine is due to the potentiation of sensory input within the limbic-hypothalamic system. In higher doses, the fatality caused by the drug may be due to the depression of the sensory input.

Amygdala↗
PubMed1978

Changes in the effects of cocaine during chronic treatment.

The principle object of the study was to identify the changes in the rat's response to cocaine which occurred during chronic administration of the drug. Doses of 20 and 35 mg/Kg cocaine were administered at intervals of 12 and 24 hours, for 300 days or until their effects proved fatal. Four main effects were observed: sensitization to cocaine's convulsant and behavioral activating properties, tolerance to its weight loss effects and decreased response duration. Convulsant sensitization occurred primarily among rats receiving the higher dose of cocaine. All other effects occurred with equal frequency in rats at both doses. None of the changes were dependent on the interval between injections.

Animals↗
PubMed1976

Conditioned suppression of an operant response using d-amphetamine as the conditioned stimulus.

The use of a drug state as a conditioned stimulus (CS) in a classical conditioning paradigm was investigated. Suppression of a single-lever food-reinforced response (variable-interval 60 s) served as an index of a classically conditioned response (conditioned suppression). d-Amphetamine (0.8 mg/kg) injections were paired with a series of inescapable shocks. Following drug-shock pairing, the effects of d-amphetamine on operant response totals was compared to effects obtained in control subjects which had received unpaired d-amphetamine and shock exposures. d-Amphetamine administered during daily operant sessions unaccompanied by shock was an effective CS for conditioned suppression of the operant response. Administration of cocaine hydrochloride (7.5 mg/kg) also produced a decrease in total responses, suggesting stimulus generalization from the shock-paired drug to a novel drug.

Animals↗
PubMed1976

Biogenic amines and the photomyoclonic syndrome in the baboon, Papio papio.

The role of biogenic amines in the proclivity of the baboon, Papio papio, to exhibit an epileptoid response to flashing light was studied. Intraventricular injections of epinephrine and norepinephrine reduced or blocked the photomyoclonic syndrome without modifying ongoing behavior. Epinephrine was effective at doses of 100 mg and more, and norepinephrine was effective at doses of 250 mg and more. Neither intraventricular injections of as much as 1.5 mg of dopamine and 1.0 mg of serotonin nor chronic systemic administration of L-dopa and L-tryptophan affected the syndrome, but reserpine, administered chronically at doses of 0.5 and 1.0 mg/kg/day, induced photosensitivity in previously nonphotosensitive animals. Seizure testing of usually photosensitive animals 12 hours after reserpine, 0.5 mg/kg, showed that the drug prevented totally or reduced the intensity of seizures in these animals. Studies of the spontaneous electroencephalogram and of visually evoked potentials of the reserpine-treated animals revealed changes in power spectra and in the averaged evoked response from the occipital area which paralleled the induction of photosensitivity. The probability that epinephrine and norepinephrine brain concentrations are essential for inhibitory modulation and control of seizures in this species is discussed.

Animals↗