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Biomedical subjects

C R Schuster

Publications and source records attributed to C R Schuster.

At least 19 recordsLinked to original sources
PubMed1992

Drug abuse research and HIV/AIDS: a national perspective from the US.

The National Institute on Drug Abuse (NIDA), the lead Federal agency charged with research on reducing the demand for illicit drugs in the US, has actively pursued the associated challenge of reducing drugs-related HIV transmission. Drug abuse-related spread of the virus occurs not only through sharing contaminated needles but also sexually to partners and perinatally from infected mothers to their offspring. Through a national research and demonstration program, NIDA supports primary AIDS risk reduction activities focused on identifying effective drug abuse prevention and treatment strategies. AIDS is increasingly a disease found in women, children, minorities, and people who live in rural areas. NIDA's efforts are clearly responsive to the changing nature of this epidemic. Among the many promising initiatives currently underway are a medications development program to find new pharmacotherapies for treating drug addiction; an array of National AIDS Outreach Demonstration Projects implementing alternative control strategies for drug abusers not attracted to or successful in drug abuse treatment; establishment of several treatment research units for designing and conducting studies on treatment effectiveness; and a variety of programs aimed at identifying and potentially reducing the risks of prenatal drug use to both mother and child. Effective dissemination of our findings is particularly critical to the overall impact of our research efforts. Collaborative activities teaming NIDA with a multitude of organizations also addressing AIDS related issues are designed to provide a synergistic impact on this complex and multifaceted public health crisis.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Recommendations for improving drug treatment.

Recognizing that drug use is both chronic and relapsing once an individual is addicted, and that treatment is effective in reducing drug use/misuse, improving drug misuse treatment is examined and research as well as practice recommendations are presented. Drug misuse treatment is now recognized in the United States to meet the expanding drug use problem and for reducing the spread of HIV. With that background, the current status of drug misuse treatment is reviewed, clinical issues are emphasized, and policy issues are noted. Recommendations include the need for uniform funding, linkage with community agencies, technology transfer, training, and expanding research and evaluation efforts.

HIV Infections↗
PubMed1990

Effects of cholecystokinin, d-amphetamine and fenfluramine in rats trained to discriminate 3 from 22 hr of food deprivation.

Attempts to assess similarities between the interoceptive stimuli of anorectic drugs and food satiation have generally been limited to human verbal reports. The purpose of the present study was to develop a procedure for assessing similarities between the interoceptive stimuli of food in the gut and various drugs known to alter food intake in rats. Rats (n = 23) were trained in a two-lever, food-reinforced, discrimination paradigm to press one lever when deprived of food for 3 hr and another lever when deprived of food for 22 hr. Criteria for stimulus control over responding were achieved after a mean of 92 (range = 26-175) training sessions. In time course tests, rats were tested when 22, 12, 6 and 3 hr food-deprived. As the number of hours of food deprivation decreased, the percentage of responses that occurred on the 3-hr food deprivation lever increased. In substitution tests, rats that were 22-hr food-deprived consistently responded as if they were 3-hr food deprived after administration of sweetened condensed milk preloads or cholecystokinin, but only occasionally after administration of water preloads, LiCl, d-amphetamine or fenfluramine. These results demonstrate that the presence of food in the gut can function as a discriminative stimulus to control lever choice in rats. Furthermore, they suggest that the discriminative stimulus effects of cholecystokinin, but not d-amphetamine or fenfluramine, are similar to those of food in the gut, and support the hypothesis that cholecystokinin plays a role in the regulation of food intake.

Animals↗
PubMed1989

Testing and abuse liability of drugs in humans.

In summary, there are a number of factors to be considered in abuse liability testing such as the purpose of the testing and its potential applications that determine which subject population we should employ. Furthermore, we should not expect to see a perfect correlation between abuse liability testing and the actual abuse of these drugs because there are many factors that will modulate or modify whether or not abuse liability becomes activated and the abuse of any specific drug becomes a social problem.

Amphetamines↗
PubMed1988

Relationship between the discriminative stimulus properties and subjective effects of drugs.

Behavioral pharmacologists have assumed that the properties of drugs that mediate their discriminative stimulus effects are related to aspects of drug actions that result in their subjective effects in humans. The basis of this assumption is examined in this chapter. Evidence to support this assumption includes the formal properties of the learning process involved in acquiring both behaviors. Although the procedures used to train animals to learn a drug discrimination are explicit, an analysis of how humans learn to attach verbal responses to unobservable internal subjective states appears to involve a similar learning paradigm. Additional evidence of the commonality of the two effects is that the results from drug discrimination studies in animals and studies evaluating subjective effects in humans yield similar drug classifications. However, when subjective drug effects are analyzed in more detail, it is clear that the concordance between the two approaches is not always good. On the other hand, when drug discrimination and subjective effects are both measured in humans, an examination of the results generated when individuals respond differently to the same drug indicates that the hypothesis that their discrimination is based upon a profile of subjective effects is supported.

Animals↗
PubMed1988

Discriminative stimulus and subjective effects of smoked marijuana in humans.

The discriminative stimulus (DS) effects of smoked marijuana were studied by training marijuana smokers to discriminate between the effects of marijuana containing 2.7% delta 9-THC (M) and marijuana containing 0.0% delta 9-THC (P). In addition to measures of discrimination responding, subjective effects were assessed with standardized mood questionnaires. The post-smoking increase in expired air carbon monoxide (CO) level was used as an index of smoke inhalation. Relative to P cigarettes, M cigarettes increased heart rate and produced changes on eight mood scales. M cigarettes were rated as harsher and more potent than P cigarettes, and produced lower levels of CO than P cigarettes. The P--M discrimination was readily acquired by most subjects. The DS effects of marijuana showed a rapid onset, appearing within 90 s from the beginning of smoking. The DS effects were dose dependent, with 0.9% delta 9-THC marijuana producing primarily placebo-appropriate discrimination responding, and 1.4% delta 9-THC marijuana producing 100% drug-appropriate responding. This experimental paradigm could be used to determine whether the DS effects of smoked marijuana would generalize to those of other psychoactive drugs.

Adolescent↗
PubMed1988

Effect of depletion of brain serotonin by repeated fenfluramine on neurochemical and anorectic effects of acute fenfluramine.

Fenfluramine is an anorectic agent in clinical use that is believed to act by enhancing 5-hydroxytryptamine (5-HT) neurotransmission. Tolerance to the anorectic properties of fenfluramine develops rapidly and long-lasting depletions of brain 5-HT have been reported to occur after repeated administration. It is possible that tolerance to fenfluramine may be related to the 5-HT depletions. Rats (n = 96), previously allowed to drink sweetened condensed milk during daily 15-min sessions, were treated with fenfluramine (6.25 mg/kg/12 hr x 4 days) or saline. Two or 8 weeks later rats were administered fenfluramine acutely (0, 1.25, 6.25 or 12.5 mg/kg; n = 6/group), tested for milk intake and sacrificed 2 hr later. Brains were removed and regions assayed for dopamine, 5-HT and metabolites. Acute administration of fenfluramine produced a dose-dependent decrease in milk intake and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in cortex, hypothalamus and hippocampus. Tolerance to the effects of acute fenfluramine on milk intake was observed in rats at 2 weeks (ED50 = 3.24 vs. 6.37 mg/kg; saline vs. fenfluramine pretreatment, respectively) and, to a lesser extent, at 8 weeks (ED50 = 2.99 vs. 4.04 mg/kg; saline vs. fenfluramine pretreatment) after the 4-day regimen of fenfluramine. Levels of 5-HT and 5-HIAA in somatosensory cortex, hypothalamus, striatum and hippocampus were depleted significantly 2 weeks after the last daily fenfluramine injection. The acute 5-HT depleting effect of fenfluramine was markedly attenuated in these regions 2 weeks after the 4-day regimen of fenfluramine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Sensitization to kappa opioid mechanisms associated with tolerance to the anorectic effects of cathinone.

To evaluate the possibility that tolerance to the anorectic effects of cathinone (CATH), an amphetamine-like compound, involves the sensitization of endogenous kappa opioid mechanisms, the influence of chronic treatment with CATH on the effects of the selective kappa opioid agonist U50488H (U50) on food and water intake was evaluated in rats. Since kappa agonists specifically increase urine output, the interaction between CATH and U50 on this physiological function was also evaluated. Acutely, CATH produced anorexia and diuresis, whereas water intake was not affected. U50 resulted in an increase in both food and water intake as well as urine output. After 9 days of daily CATH, tolerance to its anorectic effects had developed. In addition, water intake, which was not affected acutely by CATH, was significantly enhanced with respect to controls treated daily with water. In a group treated chronically with U50, its diuretic effect was unchanged, but water intake was no longer increased after 9 days of treatment. Food intake in this group remained higher than control intake for at least 19 days, but this hyperphagic effect was not detectable on day 34. On days 10 and 20 of the chronic regimen, the administration of U50 to the chronic CATH group resulted in a doubling of the hyperphagic response to U50, and this effect was naloxone-reversible. Water intake was also increased but to a lesser extent. The diuretic effect of U50 did not appear to be influenced by chronic CATH administration.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

The effects of ethanol on eye tracking in rhesus monkeys and humans.

The effects of ethanol on eye tracking function were compared in rhesus monkeys and humans using a similar experimental procedure. In Experiment 1, 3 rhesus monkeys were trained to visually track a projected image of a disk that oscillated sinusoidally along a horizontal plane on a screen. This training was accomplished using a procedure in which responses on a lever resulted in the delivery of water when the central area of the projected disk image was dimmed for a brief period. Intragastric administrations of ethanol at doses of 0.25 to 2 g/kg were tested during one-day test sessions using a cumulative dose procedure. Pursuit eye movements were disrupted at doses of 0.5 g/kg while lever pressing behavior was not disrupted until a dose of 2 g/kg was reached. In Experiment 2, pursuit eye movements of 6 humans were not disrupted when ethanol was given orally at cumulative doses of 0.25 to 1 g/kg, while microswitch pressing behavior was disrupted in some of the subjects at a dose of 0.5 g/kg. Blood ethanol levels increased in a dose-dependent manner in both species with higher levels in humans than in monkeys. The dose dependent effects observed in both species and qualitative similarities in some of the effects such as saccadic pursuit eye movements suggest that the eye tracking method employing monkeys is useful for predicting drug effects on sensory motor function in humans.

Adult↗
PubMed1987

Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain.

(+/-)-3,4-Methylenedioxymethylamphetamine (MDMA) was administered s.c. to rats (10, 20 or 40 mg/kg b. wt.) and guinea pigs (20 mg/kg) twice a day for 4 days, 2 weeks before decapitation. Norepinephrine, dopamine and serotonin (5-HT) levels were assayed in the hippocampus, hypothalamus, striatum and neocortex. In rats, MDMA produced dose-dependent reductions in 5-HT in all brain regions examined. The highest dose also reduced norepinephrine and/or dopamine in some regions. The 20-mg/kg dose of MDMA depleted 5-HT in all regions of the guinea pig brain assayed. In both species, repeated administration of 20 mg/kg of MDMA reduced the Vmax but not the Km of 5-HT uptake 2 weeks after administration. A single 40-mg/kg injection of MDMA depleted 5-HT 2 and 8 weeks after administration to rats in all regions of the brain examined except the hypothalamus. Administration of 80 mg/kg of MDMA twice a day for 2 days to rats depleted striatal 5-HT and dopamine. Brain sections from rats injected with MDMA according to this dosage regimen were stained by the Fink-Heimer method. Degenerating axon terminals and cell bodies were observed in the striatum and somatosensory cortex, respectively. These findings suggest that MDMA is toxic to serotonergic and, to a lesser extent, catecholaminergic neurons. Some neurons that do not contain these transmitters (neocortical neurons) are also affected.

3,4-Methylenedioxyamphetamine↗