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Biomedical subjects

C R Schuster

Publications and source records attributed to C R Schuster.

At least 91 records · Page 5Linked to original sources
PubMed1983

Effects of psychomotor stimulants, alone and in pairs, on milk drinking in the rat after intraperitoneal and intragastric administration.

The effects of cocaine, d-amphetamine and l-cathinone, alone and in pairs, on intake of a sweetened milk solution were determined in rats. Experimental sessions consisted of 15 min access to the milk solution daily, 7 days a week. After the determination of base-line intake, rats were assigned to one of two groups. All rats in one group received i.p. injections 15 min before the session and all rats in the other group received intragastric (i.g.) infusions 30 min before the session. A series of dose-response functions were then determined by giving a dose of a drug or a pair of drug doses once every 4 days. A wide range of doses of both drugs were tested in combination to fully characterize any interactions. When given alone, all three drugs produced dose-dependent decreases in milk intake. For each drug, higher doses were required to decrease milk intake when given i.g. than when given i.p. The decreasing order of potencies was d-amphetamine, l-cathinone and cocaine after i.p. administration and l-cathinone, d-amphetamine and cocaine after i.g. administration. In nearly every case, for both routes of administration, a drug produced dose-dependent shifts to the left of the dose-response function of the drug with which it was combined. Isobolographic analysis of the interactions indicates that d-amphetamine and l-cathinone were infra-additive (i.p.) or additive (i.g.), cocaine and d-amphetamine tended toward supra-additivity by both routes and l-cathinone and cocaine were additive or infra-additive by the i.p. route. The results of the i.g. cocaine and l-cathinone interactions could not be analyzed with isobolograms. The type of interaction was dependent on the particular drug pair, the particular dose combination tested and the route of administration.

Alkaloids↗
PubMed1982

Antagonism of gut, but not central effects of morphine with quaternary narcotic antagonists.

Naltrexone methylbromide and naloxone methylbromide, quaternary derivatives of naltrexone and naloxone respectively, are assumed to act peripherally. Both compounds reversed the intestinal stimulating effect of morphine in the dog. Naltrexone methylbromide 5 mg/kg s.c. blocked morphine-induced intestinal spike potentials for 50 min while intravenous doses caused antagonism for only 25 min. The antagonism by the s.c. route approximated that produced by naltrexone 0.2 mg/kg s.c. In morphine-dependent dogs, naltrexone methylbromide did not appear to antagonize morphine centrally in doses ranging from 0.25 to 50 mg/kg s.c. since it did not induce behavioral signs of narcotic withdrawal. Similarly, i.v. naloxone methylbromide was also able to reverse morphine-induced intestinal spike potential in dogs but the protection lasted only 25 min. In rats, naltrexone methylbromide 10 and 30 mg/kg i.p. neither reversed morphine block of PGF2 alpha-induced diarrhea nor antinociception. This suggests a lack of CNS narcotic antagonism in both test. In mice, naltrexone methylbromide, 60-720 mg/kg orally and 3-140 mg/kg i.p. failed to block morphine inhibition of prostaglandin F2 alpha-induced diarrhea. Paradoxically, in this species, 30 mg/kg s.c. of naltrexone methylbromide appeared to cross the blood-brain barrier since this dose reversed morphine-induced antinociception. In conclusion, naltrexone methylbromide effectively antagonizes the acute gut stimulating effect, but not the chronic behavioral effect of morphine administration in dogs. Based upon the antinociception test, naltrexone methylbromide does not cross the blood-brain barrier in rats but may in mice. Morphine inhibits prostaglandin F2 alpha-induced diarrhea by a central mechanism in rodents.

Animals↗
PubMed1982

Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain.

Numerous recent studies indicate that when amphetamines are administered continuously or in high doses, they exert long-lasting toxic effects on dopamine (DA) neurons in the central nervous system (CNS). Specifically, it has been shown that amphetamines can decrease the content of brain DA, reduce the number of synaptosomal DA uptake sites and selectively depress the in vitro activity of neostriatal tyrosine hydroxylase (TH). To date, however, anatomical evidence of DA neuronal destruction following amphetamines has not been reported. In this study, chemical methods were used in conjunction with the Fink-Heimer method which allows for the selective silver impregnation of degenerating nerve fibers, in order to determine whether methylamphetamine, a potent psychomotor stimulant often abused by man, causes actual DA neural degeneration. It has been found that methylamphetamine induces terminal degeneration along with correlative DA neurochemical deficits in the neostriatum and nucleus accumbens; furthermore, that in cresyl violet-stained sections of the substantia nigra (SN), pars compacta, and ventral tegmental area (VTA), there is no evidence of cell body loss in rats in which 50-60% of neostriatal DA terminals have been destroyed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1982

Altered sensitivity to d-methylamphetamine, apomorphine, and haloperidol in rhesus monkeys depleted of caudate dopamine by repeated administration of d-methylamphetamine.

The long-term neurochemical and behavioral effects of repeated d-methylamphetamine (d-MA) administration were investigated using four male rhesus monkeys trained to lever-press for food on a DRL-40s schedule of reinforcement. Dose-response curves for d-MA (0.0625-2.0 mg/kg), apomorphine (0.025-0.4 mg/kg), and haloperidol (0.005-0.04 mg/kg) on responding showed that repeated d-MA administration (0.5-16.0 mg/kg/day) decreased sensitivity to d-MA and to apomorphine but increased sensitivity to haloperidol. At 3-6 months after the last injection of d-MA, a 48.1% decrease in caudate dopamine (DA) was observed, with the frontal cortex, midbrain, and pons-medulla showing no significant change. A trend toward increasing concentrations of norepinephrine was noted in the same brain areas, but only in the frontal cortex did this change reach significance. Specific binding of 3H-spiroperidol to caudate membrane preparations was not changed, while the Vmax of the caudate DA re-uptake process declined 32%, with no change in Km. These results suggest that exposure of DA neurons in the caudate nucleus to high concentrations of d-MA can lead to nerve terminal degeneration.

Animals↗
PubMed1982

The effects of cocaine in a gustatory avoidance paradigm: a procedural analysis.

When the presentation of a novel food to a rat is followed by the injection of certain compounds, the animal consumes less of that food on subsequent presentations. Conflicting results have been obtained when cocaine is used in this gustatory avoidance paradigm. In the present study, fluid intake of rats was limited to a single presentation, seven days a week. Following the determination of baseline water intake, sweetened fluid was given during the session following the determination of baseline water intake, sweetened fluid was given during the session followed by an injection of cocaine. In Experiment 1, 24.0 mg/kg cocaine-fluid pairings occurred on alternate days with two-bottle preference tests occurring between pairings. Animals treated with cocaine had lower preference ratios than saline controls although both groups consumed more novel fluid than tap water. In Experiment 2, preexposure to the fluid prior to pairing it with cocaine eliminated differences between cocaine and saline treated rats. In Experiment 3 no effect of cocaine on novel fluid consumption was seen in male or female rats when 24.0 mg/kg cocaine-fluid pairings were given for five consecutive days. In addition, 36 mg/kg cocaine when paired with novel fluid every other day failed to induce an avoidance response in Experiment 4. These results indicate that cocaine is a weak avoidance-producing agent in the gustatory avoidance paradigm, and suggests the need for a standardized procedure for studying drugs in this paradigm.

Animals↗
PubMed1982

Experimental studies of the abuse potential of d, l-glaucine. 1.5-phosphate in rhesus monkeys.

d-Glaucine is an alkaloid derived from Glaucium flavum, which is as effective as codeine as an antitussive. d, l-Glaucine. 1.5 phosphate is a synthetic compound related to d-glaucine. The ability of d, l-glaucine.1.5 phosphate to maintain responding in rhesus monkeys was assessed in 2 procedures. In the first responding was maintained under a fixed-ratio 10 schedule of codeine delivery during daily 3-hr sessions. When d, l-glaucine.1.5 phosphate (0.05-0.4 mg/kg) was substituted for codeine, responding was not maintained. In the second procedure, monkeys given 23-hr/day access to 0.5-1.0 mg/kg under a fixed-ratio schedule did not self-administer d,l-glaucine.1.5 phosphate above saline levels even after a 21-day period of programmed injections. Following the period of programmed injections, there were not signs of opiate withdrawal following the administration of naloxone. These results indicate that the abuse potential of d,l-glaucine.1.5 phosphate is low relative to codeine.

Animals↗
PubMed1982

A comparison of the central and peripheral effects of atropine on force lever performance.

The central and peripheral effects of atropine, a muscarinic antagonist, on motor control were tested in a force lever apparatus. Three rhesus monkeys were trained to extend their arms through a tube and press a manipulandum with between 25 and 40 grams of force for 3 continuous seconds. Responding was maintained by the delivery of 1.5 ml of water. Single injections of atropine sulfate or atropine methylnitrate (a quaternary derivative) of atropine which does not cross the blood brain barrier) were given 30 min prior to the session. Atropine sulfate disrupted force lever performance in a dose related fashion. Atropine methylnitrate had little or no effect on responding. The effects of atropine on motor control as measured in this procedure, therefore, appear to be centrally mediated.

Animals↗
PubMed1982

Neurochemical similarities between d,l-cathinone and d-amphetamine.

Cathinone, the principal alkaloid of Khat, was compared to the psychomotor stimulant d-amphetamine on a number of neurochemical measures. Like d-amphetamine, d,l-cathinone released and blocked the uptake of tritiated dopamine (DA) in synaptosomal preparations. In addition, repeated high doses of d,l-cathinone produced long-lasting DA depletions in various rat brain regions and decreased the number of synaptosomal DA uptake sites in a manner similar to that seen after repeated d-amphetamine administration. Importantly, this DA neurotoxic effect of d,l-cathinone, like that of d-amphetamine, is selective since regional brain levels of norepinephrine (NE) or serotonin (5-HT) are not altered on a long-term basis by repeated administration of d,l-cathinone. These findings are discussed with reference to the current practice of Khat leaf chewing by people in north-eastern Africa.

Alkaloids↗
PubMed1982

Cocaine self-administration in humans.

Studies are described in which normal healthy volunteers were tested with a wide range of intravenous doses of cocaine of d-amphetamine. Physiological measurements included heart rate, electrocardiogram, blood pressure, respiration rate, and temperature. Behavioral measures included the use of the Profile of Mood States to assess drug-related mood changes, the Addiction Research Center Inventory to assess drug-related changes in verbal reports of their effects, and ratings comparing drug effects of experimentally administered and "street" drugs. In addition, plasma levels of cocaine were monitored to correlate with physiological and behavioral effects. Subjects were also allowed to choose between intravenous injections of cocaine or saline. As with nonhuman research subjects, cocaine was consistently chosen over saline by all subjects tested. The self-administration data and data describing the subjective and cardiovascular spectrum of action were combined to yield a more complete profile of cocaine's action in humans.

Adult↗
PubMed1982

Behavioral tolerance and cross-tolerance to dl-cathinone and d-amphetamine in rats.

The effects of dl-cathinone (0.25-48 mg/Kg, i.p. and d-amphetamine (0.25-8.0 mg/kg, i.p.) on milk intake in rats were determined before, during and after a period of repeated daily administration of dl-cathinone. Experimental sessions consisted of 15-min access to a sweetened milk solution each day. 7 days a week. After the determination of the acute effects of dl-cathinone and d-amphetamine on milk intake, rats were injected daily with either 4.0 mg/kg of dl-cathinone 15 min before each session and saline 15 min after each session; or saline 15 min before each session and 4.0 mg/kg of dl-cathinone 15 min after each session. Milk intake returned toward base-line levels for animals receiving daily dl-cathinone before the session over a period of 16 sessions, and remained slightly decreased compared to animals that received postsession injections. Dose-response functions for dl-cathinone and d-amphetamine were then redetermined by substituting a test dose for the usual presession injection once every 4 to 5 days. In animals that were receiving presession dl-cathinone, both drugs had less effect, indicating the development of tolerance to dl-cathinone and cross tolerance to d-amphetamine. The development of tolerance to the suppression of milk drinking was contingent upon the relationship of the time of the daily injection to milk availability. Animals that were receiving dl-cathinone after the session did not develop tolerance but were more sensitive to the effects of both drugs on milk intake. Dose-response functions for both drugs determined after 10 drug free days were similar to the initial dose-response functions, indicating the transient nature of the tolerance and supersensitivity.

Alkaloids↗
PubMed1981

Conditioned gustatory avoidance induced by three cholinergic agents.

Conditioned gustatory avoidance of sweetened condensed milk was induced in rats by drugs which differentially affect the cholinergic nervous system. After baseline water intake during a 15 minute daily session was established, sweetened condensed milk was presented in place of water, followed 15 minutes later by an IP injection of saline, physostigmine (0.5 mg/kg), atropine (25 mg/kg) or mecamylamine (25 mg/kg). Three presentations of milk were given, alternating daily with a water presentation. Atropine, a muscarinic blocker, and mecamylamine, a nicotinic blocker, both produced a strong avoidance. Physostigmine, an indirect agonist, produced a less pronounced avoidance at the dose employed. This study indicates that cholinergic agonists and antagonists are capable of inducing conditioned gustatory avoidance.

Animals↗