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Biomedical subjects

C R Schuster

Publications and source records attributed to C R Schuster.

At least 109 records · Page 6Linked to original sources
PubMed1981

Dopamine depletion by 6-hydroxydopamine prevents conditioned taste aversion induced by methylamphetamine but not lithium chloride.

Specific lesions of the central dopaminergic system produced by intraventricular injections of 6-hydroxydopamine with pargyline and desmethylimipramine pretreatment significantly attenuated conditioned taste aversions to a sweetened-condensed milk solution induced by methylamphetamine. Identically treated rats formed an aversion to the milk solution when lithium chloride was utilized. These results suggest that the methylamphetamine-induced aversion is dependent upon intact dopaminergic neurons.

Animals↗
PubMed1981

Neurochemical consequences following administration of CNS stimulants to the neonatal rat.

The possible induction of long-lasting catecholamine depletions in discrete brain regions by psychomotor stimulant drugs was examined in neonatal rats. Three agents, methylamphetamine, d-amphetamine, and methylphenidate were administered to groups of rat pups from days 10 to 40 of life. Pups were killed 2 weeks beyond the last drug administration. Catecholamine levels of various brain regions from groups of rats receiving 12.5, 25 or 50 mg/kg/day of each drug were compared with levels of vehicle treated pups. Both methylamphetamine and d-amphetamine at the higher doses induced long-lasting dopamine depletions in the caudate of rat pups. Methylphenidate had no long-term effect on dopamine while norepinephrine levels were not altered by any treatment.

Animals↗
PubMed1981

The aversive stimulus properties of repeated infusions of cocaine.

When the presentation of a novel food to a rat is followed by the administration of certain compounds, including psychomotor stimulants, the animal consumes less of the food on subsequent presentations relative to an animal administered saline. This phenomenon has been termed gustatory avoidance conditioning. Conflicting results have been obtained when cocaine is used in this procedure. Therefore, the possibility that the weak efficacy of cocaine in this paradigm is due to its relatively short duration of action was investigated. Fluid intake was limited to a single 15 min presentation, seven days a week. Following the determination of baseline water in take sweetened milk was given during the session followed by a series of infusions of cocaine through chronic indwelling peritoneal catheters. Four infusions, spaced 15 min apart, of 9.0 mg/kg cocaine induced an avoidance response, while one infusion of 36 mg/kg cocaine followed by three saline infusions did not. This supports the hypothesis that the low efficacy of cocaine in this paradigm is due, at least in part, to its short duration of action.

Animals↗
PubMed1981

Behavioral effects of thebaine in the rhesus monkey.

Three experiments were conducted with rhesus monkeys to assess some behavioral effects of the opium alkaloid, thebaine, in relation to its dependence liability. The concurrent intramuscular administration of naloxone did not antagonize the rate-decreasing effects of thebaine on a fixed-ratio (FR) schedule of food-reinforced responding. Animals trained to self-administer codeine (0.3 mg/kg/inj) on an FR 30 schedule did not self-administer thebaine (0.003-1.0 mg/kg/inj) at rates comparable to these of codeine. Rates were minimally above those of saline at 0.3 mg/kg inj. Monkeys given 23 hrs/day continuous access to 1.0 mg/kg/inj thebaine did, however, self-administer the drug at rates significantly higher than those maintained by saline, but not as high as those supported by 2.0 mg/kg/inj codeine. Two animals self-administering thebaine did not show any signs of withdrawal when injected with 0.1-1.0 mg/kg of naloxone or when saline was substituted for thebaine. A third monkey showed a severe reaction leading to death following an injection of 1.0 mg/kg naloxone.

Animals↗
PubMed1981

The effects of dl-cathinone in a gustatory avoidance paradigm.

When the presentation of a novel food to a rat is followed by the injection of a certain compounds, including many psychomotor stimulants, the animal consumes less of that food on subsequent presentations compared to an animal injected with saline. This phenomenon has been termed gustatory avoidance conditioning. The effect of dl-cathinone, a psychomotor stimulant drug structurally similar to amphetamine, was determined in this paradigm. Fluid intake was limited to a single 15 min presentation, seven days a week. Following the determination of baseline water intake, sweetened milk was presented for five consecutive sessions. There were six groups of rats with each group receiving a different dose of cathinone (0--16.0 mg/kg) five min after the session each day. Following these five days of milk-cathinone pairings, milk intake was significantly decreased only in the rats receiving 16 mg/kg. These results indicate that cathinone which is nearly as potent as amphetamine in many other behavioral measures, is less potent in inducing gustatory avoidance responses.

Alkaloids↗
PubMed1981

An analysis of drug-seeking behavior in animals.

This article reviews the literature on the behavioral aspects of opiate dependence. Available data on the variables affecting drug-maintained behavior are presented. These variables are: (a) reinforcement variables, including parameters such as delay, magnitude, rate and duration of the reinforcing stimulus; (b) antecedent conditions, such as deprivation and satiation; (c) organismic variables, such as genotype, species, sex and age; (d) current environmental contingencies, such as the schedule of reinforcement in effect, or extinction; and (e) such experiential variables as pharmacological and behavioral history of the organism. The review ends with a discussion of the implications of these variables for the treatment of drug abuse.

Age Factors↗
PubMed1981

Acute tolerance to cocaine in humans.

It has been shown that there is a dose-response relationship between blood levels of intravenously injected cocaine and magnitude of evoked heat rate (Javaid et al. 1978). This relationship also holds for inhaled cocaine while plasma levels are increasing, but the cardiovascular effects of the drug dissipate more rapidly than cocaine disappears from the plasma. This suggests that the repeated administration or sustained blood level of cocaine might produce an acute tolerance. Using an intranasal route of administration it is possible to maintain cocaine blood levels for a substantial period of time after heart rate begins to decrease from its peak levels. If an intravenous dose is then administered on top of this preexisting blood level, the effects of this second dose can be compared to the same dose administered to subjects with no preexisting blood level.

Cocaine↗
PubMed1981

Effect of antimorphine antibodies on an in vitro correlate of antagonist-precipitated opiate abstinence.

Antimorphine globulin was used to study the mechanism by which naloxone produces a contracture in ileal strips removed from morphine pellet-implanted guinea pigs. Although the antibodies effectively reversed the depressant actions of morphine on electrically stimulated contractions in both naive and tolerant tissues, neither monkey antimorphine (Kd = 1.43 x 10(-7)M) nor goat antimorphine (Kd = 1.36 x 10(-9)M) were able to elicit a naloxone-like contracture. The rate of attenuation of tissue sensitivity to naloxone was measured and no changes were observed after incubation in the presence of monkey antimorphine globulin. High-affinity goat antimorphine globulin, however, was able to accelerate the rate of attenuation of tissue sensitivity to naloxone. The naloxone contracture was accompanied by release of material reactive with morphine antiserum in a radioimmunoassay. The quantities of material were in excess of what could be bound by opiate receptors present in the tissue. Possible mechanisms of naloxone sensitivity observed in the isolated ileum are discussed.

Animals↗
PubMed1981

A comparison of the behavioral effects of l- and dl-cathinone and d-amphetamine.

The leaves of the Catha edulis plant (Khat) are chewed extensively by inhabitants of several African and Arab countries. It has been postulated that the behavioral effects of Khat are similar to those of amphetamine and that one of its components, cathinone, is the principal active alkaloid. In the first study, the ability of i.v. l-cathinone (0.0008-0.05 mg/kg/infusion), dl-cathinone (0.0016-0.1 mg/kg/infusion) and d-amphetamine (0.0016-0.025 mg/kg/infusion) to maintain responding under a fixed-ratio 10 schedule of delivery was determined. All three drugs functioned as positive reinforcers. Relative to amphetamine, lower doses of l-cathinone maintained responding, whereas the function for dl-cathinone was shifted to the right of amphetamine. However, potency comparisons are complicated by the fact that the dose-infusion functions for both l- and dl-cathinone were broader and peaked at higher rates than those generated by d-amphetamine. Because response rates under ratio schedules of drug delivery are determined by several properties of a drug, the relative potency of cathinone and d-amphetamine was investigated further. In a second experiment, the effects of i.v. l- and dl-cathinone (0.025-3.2 mg/kg) and d-amphetamine (0.0125-1.6 mg/kg) on responding maintained under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food delivery were determined in three monkeys. Although there were some increases in overall rats, these drugs primarily produced dose-dependent decreases in responding under both schedules. d-Amphetamine was 2 to 4 times more potent than l- and dl-cathinone which were equipotent. This may indicate that the lower rates of responding maintained by d-amphetamine in the first experiment were due to its greater potency in disrupting responding.

Alkaloids↗
PubMed1980

Long-term effects of repeated methylamphetamine administration on dopamine and serotonin neurons in the rat brain: a regional study.

Repeated high doses (25 and 100 mg/kg) of methylamphetamine produce long-term depletions of both dopamine (DA) and serotonin (5-HT) in the rat brain. In the DA system, depletions are most pronounced in the neostriatum and substantia nigra, with decreased levels in these two regions being significantly correlated. Within the 5-HT system, levels are most reduced in the amygdala, frontal cortex and neostriatum. When both the DA and 5-HT depleting actions of methylamphetamine are considered, the hypothalamus stands out as one of the more resistant brain regions. The regional pattern of reduced 5-HT levels following methylamphetamine is similar to that seen after p-chloroamphetamine. After both methylamphetamine and p-chloroamphetamine, a loss of 5-HT synaptosomal uptake sites occurs. Serotonergic systems are more sensitive than DA systems to the apparent neurotoxic actions of methylamphetamine.

Amphetamines↗
PubMed1980

Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine.

Repeated administration of high doses of methamphetamine produced long-term decreases in dopamine (DA) levels and in the number of DA uptake sites in the rat striatum. These two effects were dose-related and did not appear to be due to the continued presence of drug in striatal tissue. Long-lasting depletions induced by methamphetamine were selective for striatal DA neurons since norepinephrine (NE) levels in all of the rat brain regions examined were not changed on a long-term basis by methamphetamine treatments. Supersensitivity of DA receptors did not accompany the loss of striatal DA and its uptake sites.

Animals↗
PubMed1980

Cocaine effects in sleep-deprived humans.

Eight normal healthy volunteers were tested in a reaction-time task and a work-output task after 24 and 48 h of sleep deprivation with and without 96 mg of inhaled cocaine. Cardiovascular changes and verbal report of mood change and drug effect were also monitored. Sleep deprivation produced a decrement in reaction-time performance which was reversed by inhalation of cocaine. Heart rate increased after cocaine both under non sleep-deprived conditions and sleep-deprived conditions. The magnitude of the drug-induced heart rate was, however, lower when subjects were deprived of sleep for 48 h. Verbal reports of cocaine effects were similar to those reported for amphetamine, with no evidence supporting the idea of a postdrug depression immediately after the acute effects of the drug dissipated, although some rebound effects were noted 8 h after drug administration.

Adult↗
PubMed1980

A single dose study of nabilone, a synthetic cannabinoid.

The effects of single oral doses of nabilone, a synthetic cannabinoid, were studied in four anxious volunteer subjects. Each subject had two exposures to placebo and three dose levels of nabilone at 1 week intervals in a single blind balanced Latin square design after the nabilone dose range was determined by each subject's response to a test dose. The Profile of Mood States (POMS), a self-rating adjective checklist, was used as the quantitative measure of subjective effects. The subjects performed a continuous avoidance procedure. High doses (4 or 5 mg) of nabilone produced orthostatic hypotension. Small dose-related increases in heart rate also occurred. Despite the occurrence of highly significant levels of subjective sedation, there were no significant effects of nabilone on behavior maintained by the continuous avoidance procedure. Two of these subjects experienced an anti-anxiety effect from low (1 or 2 mg) nabilone doses, but there was no statistically significant effect on the mean POMS anxiety factor for the group as a whole. In a follow-up experiment, four other anxious subjects received comparatively lower doses of nabilone. In these subjects there were no important effects on blood pressure or heart rate, and also no anti-anxiety effects.

Adult↗
PubMed1980

The effects of dopaminergic agents on the locomotor activity of rats after high doses of methylamphetamine.

Treatment of rats with 100 mg/kg/day of methylamphetamine for four days produced long lasting (16 week) depletions of central nervous system levels of dopamine but not of norepinephrine. This methylamphetamine treatment also attenuated the ability of methylamphetamine and apomorphine to produce increases in locomotor activity without shifting the dose-response curve to the right or left. These rats underwent significant decreases in activity after lower doses of haloperidol while the response to L-Dopa was virtually unchanged.

Animals↗
PubMed1980

Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudate.

Long-lasting depletion of dopamine and concomitant loss of dopamine uptake sites follow repeated administration of methylamphetamine to rats. We found similar effects after similar treatment with d-amphetamine, but not after treatment with methylphenidate. Methylphenidate also failed to produce long-term depletion of regional catecholamine levels in rhesus monkeys. These long-lasting alterations of the dopaminergic system suggest that amphetamines or their metabolites have toxic interactions with dopaminergic neurons, which do not occur with methylphenidate.

Animals↗
PubMed1979

The effects of chlorpromazine and pentobarbital on behavior maintained by electric shock or point loss avoidance in humans.

Human volunteer subjects were trained to press a lever to avoid or escape electric shock or loss of points which could be redeemed for money at the termination of the study. The effects of pentobarbital and chlorpromazine on avoidance and escape behavior were compared. Both aversive stimuli maintained behavior which was differentially sensitive to these two drugs. Chlorpromazine caused a decrease in avoidance responding at doses which had little effect on escape responding. Pentobarbital, in contrast, suppressed avoidance responding at doses which also had a suppressant effect on escape responding.

Adult↗
PubMed1979

The effects of methamphetamine on fine motor control in rhesus monkeys.

Six rhesus monkeys were trained to extend their arms through a tube to press a lever with between 25 and 40 g of force for 3 or 5 sec. Responding was maintained by the delivery of 1.5 cc of water. Stimulus lights indicated whether the exerted force was below 25 g. between 25 and 40 g (i.e., correct) or above 40 g. Sessions were terminated after 50 water deliveries or 30 min had elapsed. Performance was well-maintained in all monkeys. Allowing the animals access to water prior to the session had no effect on performance. Discontinuing sessions for two weeks disrupted some aspects of performance but responding improved within 5 sessions. Single injections of methamphetamine (0.06-0.5 mg/kg) were given IM 20 min prior to the session. The highest dose of 0.5 mg/kg totally eliminated responding. Lower doses decreased rate of responding somewhat and increased phasic activity (i.e., tremors) in a dose-dependent manner. The procedure seems ideally suited for investigating the effects of psychotropic drugs on fine motor control in rhesus monkeys.

Animals↗