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Biomedical subjects

C R Schuster

Publications and source records attributed to C R Schuster.

At least 73 records · Page 4Linked to original sources
PubMed1985

Specific antagonism by RO 15-1788 of benzodiazepine-induced increases in food intake in rhesus monkeys.

Food intake of rhesus monkeys was limited to a single daily 2 hr session of banana flavored pellet availability, seven days a week. Following stabilization of intake, the effects of intragastric bromazepam, diazepam and pentobarbital, when given alone, were determined by delivering a dose twice weekly, 60 min before the session. Dose-dependent increases in food intake were observed with the following descending order of potencies: bromazepam, diazepam and pentobarbital. RO 15-1788 (0.5-1.0 mg/kg, IM), when given alone, five min before the session had no effect on food intake. When given in combination with bromazepam and diazepam, RO 15-1788 completely blocked the increases in food intake observed when the benzodiazepines were given alone. The specificity of this antagonism was shown by the failure of RO 15-1788 to alter the food intake increases induced by pentobarbital. These results confirm and extend previous reports of the specific antagonism of benzodiazepine behavioral effects by RO 15-1788 to an additional species and another behavioral effect of benzodiazepines.

Animals↗
PubMed1985

'Hangover' effects the morning after marijuana smoking.

Thirteen male marijuana smokers participated in a study to determine whether marijuana smoked in the evening would result in measurable subjective or other behavioral effects the following morning. Subjects smoked either active (2.9% delta 9THC) or placebo (0.0% delta 9THC) marijuana cigarettes according to a standardized smoking regimen. Smoke inhalation was monitored by measuring expired air carbon monoxide (CO) levels before and after smoking. Acutely, active marijuana produced significant changes in heart rate, CO level, various measures of subjective effects, and behavioral tasks of card sorting, free recall and time production. When the test battery was repeated the following morning (approx. 9 h after smoking), significant changes were observed on two subjective effects scales and on the time production task after active, but not placebo, marijuana. These apparent 'hangover' effects were different from the acute effects of marijuana. The findings suggest that marijuana smoking can produce residual (hangover) effects the day after smoking. The precise nature and extent of these effects, as well as their practical implications, remain to be determined.

Adult↗
PubMed1985

Behavioral effects of selected opiates and phencyclidine in the nondependent and cyclazocine-dependent rhesus monkey.

Tolerance to the behavioral effects of selected opiate compounds (cyclazocine, ketocyclazocine, naloxone and the stereoisomers of N-allylnormetazocine) and phencyclidine was evaluated using cumulative dosing procedures in rhesus monkeys responding under a fixed-ratio (FR) schedule of food presentation. Initially, the i.v. injection of graded doses of each drug in 8-min time-out periods preceding sequential FR periods decreased responding after each time-out in dose-related fashion. Subsequently, daily administration of up to 11 mg/kg of cyclazocine led to an approximately 16 to 32-fold rightward shift in the dose-effect curves for cyclazocine and ketocyclazocine and an approximately 4-fold rightward shift in the dose-effect curves for phencyclidine and (+)-N-allynormetazocine. In contrast, the dose-effect curves for naloxone and (-)-N-allynormetazocine were generally unchanged or shifted leftward. Termination of daily cyclazocine administration produced signs of withdrawal which disappeared over several days in all monkeys. These included emesis, frequent aggressive display and disruption of schedule-controlled performance. Present results suggest that the rate-decreasing effects of racemic cyclazocine involve mechanisms distinct from those mediating the rate-decreasing effects of naloxone or (-)-N-allynormetazocine. The differing degrees of cross-tolerance produced to the rate-decreasing effects of ketocyclazocine and of phencyclidine and (+)-N-allynormetazocine also suggest that the latter compounds produce behavioral effects to some extent through mechanisms distinct from those through which ketocyclazocine is effective.

Animals↗
PubMed1985

Acute tolerance development to the cardiovascular and subjective effects of cocaine.

Eight normal adult volunteer subjects received an intranasal pretreatment of either 4 (placebo) or 96 mg of cocaine. Sixty minutes later 16, 32 or 48 mg of cocaine was injected i.v. Cocaine plasma levels were determined periodically over a 2-hr period and both cardiovascular effects and verbal report of drug effects were monitored for 8 hr daily. The plasma concentrations of cocaine were always related to the dose administered. When i.v. cocaine was given after a 96-mg intranasal pretreatment, the increase in heart rate was not as great as when an i.v. injection followed a 4-mg inhalation. Comparable changes were obtained in subjective effects as measured on the Addiction Research Center Inventory, the Profile of Mood States and a subjective effects questionnaire. These results suggest that there is a decrease in physiological and subjective effects of cocaine when administered repeatedly in humans. This acute tolerance appeared to have dissipated within 24 hr.

Adult↗
PubMed1984

Further evidence that amphetamines produce long-lasting dopamine neurochemical deficits by destroying dopamine nerve fibers.

Methamphetamine and amphetamine were continuously administered to rats for 3 days by means of subcutaneously implanted osmotic minipumps. The total daily dose of each drug was approximately 4 mg/day. Dopamine, norepinephrine and serotonin determinations two weeks later indicated that both amphetamines produced a selective striatal dopamine depletion. Anatomical studies indicated that this depletion was associated with striatal nerve fiber degeneration. To determine whether this fiber degeneration induced by amphetamines was dopaminergic, the long-lasting dopamine depletion produced by methamphetamine was antagonized with alpha-methyl-para-tyrosine. This prevented the appearance of nerve fiber degeneration after methamphetamine. These findings suggest that amphetamines produce a long-term striatal dopamine depletion by destroying striatal dopamine nerve fibers.

Amphetamine↗
PubMed1984

Nerve terminal degeneration after a single injection of D-amphetamine in iprindole-treated rats: relation to selective long-lasting dopamine depletion.

A single injection of D-amphetamine has recently been shown to produce long-lasting dopamine (DA) deficits in rats pretreated with iprindole, an agent which interferes with the metabolism of amphetamine and prolongs its half-life. The basis for these persistent DA deficits has not been determined. The present results suggest that amphetamine produces prolonged DA depletions in iprindole-treated rats by destroying DA nerve terminals.

Animals↗
PubMed1984

Response of monkeys to intragastric preloads: limitations on caloric compensation.

Food intake of rhesus monkeys was limited to a single daily 2 hr session of banana flavored pellet availability, seven days a week. Following stabilization of intake, the effects of liquid preload meals (0-80% of normal meal size) delivered through nasogastric tubes or chronic indwelling intragastric (IG) catheters were determined during test sessions by delivering preloads 15 min prior to the session. Monkeys compensated for preloads by decreasing intake by an amount nearly equal to the energy content of the preload. As the time between the delivery of an IG preload equivalent to 40% of a normal day's intake and the beginning of the session was increased, accuracy of compensation decreased. Monkeys also did not compensate for a chow meal given 2 hr before the session and compensation did not improve when this meal was given for ten consecutive days 2 hr before a session. In addition, an IG preload equivalent to 40% of a normal day's intake was given 20 hr before the session under two conditions: two hours after or immediately after the session on the day preceding testing. Only the preload given immediately after the session decreased food intake 20 hr later. However, a control volume of tap water delivered immediately after the session also decreased food intake 20 hr later. Finally, monkeys did not compensate for deprivation experienced one day by increasing their food intake the following day. In sum, these results indicate that under these conditions, the rhesus monkey does not regulate its food intake as accurately as previously reported.

Animals↗
PubMed1984

Effects of methamphetamine on atropine-induced conditioned gustatory avoidance.

The repeated administration of high doses of methamphetamine (MA) has been shown to cause monoaminergic damage in rhesus monkeys and rats. In view of the purported interaction between central cholinergic and monoaminergic systems, rhesus monkeys and rats previously exposed to high doses of MA were tested in conditioned gustatory avoidance studies with atropine (a muscarinic blocker) as the unconditioned stimulus. It was observed that both rhesus monkeys and rats previously exposed to high doses of MA exhibited less of an atropine-induced avoidance than control monkeys and rats. To control for the nonspecific effects of prior exposure to stimulants, an additional group of rats previously exposed to high doses of methylphenidate ( a stimulant shown to not cause catecholaminergic damage) was tested in the same paradigm. The methylphenidate treated rats showed no change in sensitivity to atropine in the conditioned gustatory avoidance paradigm as compared to control rats which indicated that prior exposure to the nonspecific effects of a stimulant without monoaminergic alterations does not alter the sensitivity of atropine's avoidance-inducing properties. The results of these experiments imply that atropine's avoidance-inducing properties may in part be mediated through the monoaminergic system.

Animals↗
PubMed1983

Alpha-methyltyrosine attenuates and reserpine increases methamphetamine-induced neuronal changes.

The repeated administration of methamphetamine to rats has been shown to cause a long-lasting depletion of dopamine in various brain regions. In the first study, the effects of pretreatment with alphamethyltyrosine (AMT) or reserpine on the long-lasting methamphetamine-induced dopamine depletion were examined. In the second study, the effects of AMT and reserpine on central dopamine levels were measured in rats previously treated with methamphetamine. Pretreatment with AMT attenuated the long-lasting dopamine depletion induced by methamphetamine, whereas, pretreatment with reserpine increased the depletion. The acute effects of AMT and reserpine on brain dopamine were not altered when administered two weeks after the last methamphetamine injection.

Animals↗
PubMed1983

Effects of phencyclidine, secobarbital and diazepam on eye tracking in rhesus monkeys.

Rhesus monkeys were trained to track a moving disk using a procedure in which responses on a lever were reinforced with water delivery only when the disk, oscillating in a horizontal plane on a screen at a frequency of 0.4 Hz in a visual angle of 20 degrees, dimmed for a brief period. Pursuit eye movements were recorded by electrooculography (EOG). IM phencyclidine, secobarbital, and diazepam injections decreased the number of reinforced lever presses in a dose-related manner. Both secobarbital and diazepam produced episodic jerky-pursuit eye movements, while phencyclidine had no consistent effects on eye movements. Lever pressing was disrupted at doses which had little effect on the quality of smooth-pursuit eye movements in some monkeys. This separation was particularly pronounced with diazepam. The similarities of the drug effects on smooth-pursuit eye movements between the present study and human studies indicate that the present method using rhesus monkeys may be useful for predicting drug effects on eye tracking and oculomotor function in humans.

Animals↗
PubMed1983

The effect of d-amphetamine and haloperidol alone and in combination on milk drinking in rats.

The effects of d-amphetamine (0.5-4.0 mg/kg IP) and haloperidol (0.015-1.0 mg/kg IP) alone and in combination on intake of a sweetened milk solution were determined in rats. Experimental sessions consisted of a 15-min access to the milk solution once a day, 7 days a week. d-Amphetamine was administered 15 min prior to the session and haloperidol was administered 60 min prior to the session. The interaction of these compounds was determined by repeated determination of the dose-response function for d-amphetamine in combination with different doses of haloperidol. When given alone, each drug produced a dose-dependent decrease in milk intake. In combination with haloperidol, the decrement caused by d-amphetamine was shifted to lower doses in a dose-dependent manner. Isobolographic analysis of the interaction indicates that the intermediate doses (0.03-0.06 mg/kg) of haloperidol were additive and the highest doses (0.12-0.25 mg/kg) of haloperidol were infraadditive with d-amphetamine. Dose-dependent neuropharmacological actions of these compounds may account for dose-dependent interactions.

Animals↗
PubMed1983

Fluoxetine increases long-lasting neostriatal dopamine depletion after administration of d-methamphetamine and d-amphetamine.

Repeated administration of large doses of d-methamphetamine produce long-lasting depletion of brain dopamine (DA) and serotonin (5-HT), as well as persistent decreases in the activity of their respective biosynthetic enzymes, tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH). The present results indicate that the inhibitor of 5-HT uptake fluoxetine, prevented the long-term depletion of 5-HT produced by large doses of methamphetamine (15 mg/kg X 5, 6 hr apart) in the neostriatum and hippocampus, while simultaneously augmenting the depletion of DA produced by this drug in the neostriatum. Fluoxetine also enhanced the prolonged neostriatal depletion of DA produced by a comparable regimen of d-amphetamine. In these doses (15 mg/kg X 5,6 hr apart), d-amphetamine did not produce long-lasting depletion of 5-HT in either the neostriatum or hippocampus. Larger depletion of DA after the amphetamines had been administered in the fluoxetine pretreated animal were associated with a transient increase in the brain levels of methamphetamine and amphetamine. This suggests that fluoxetine may inhibit the metabolism of amphetamines.

Animals↗
PubMed1983

Increased dopamine metabolism in the rat neostriatum after toxic doses of d-methylamphetamine.

Rats were given repeated large doses of d-methylamphetamine (d-MA) which have been shown to destroy a fraction of nigrostriatal dopamine (DA) nerve terminals. Two to three weeks later, the synthesis of DA in the remaining neostriatal DA terminals was examined by measuring the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of L-aromatic amino acid decarboxylase by 3-dihydroxybenzylhydrazine (NSD 1015). The release of DA from surviving DA terminals was also examined by measuring the steady-state level of 3,4-dihydroxyphenylacetic acid (DOPAC). Both the rate constant of the synthesis of DA and the DOPAC/DA ratio were increased in the neostriatum of rats with large depletions of neostriatal DA. These findings suggest that both synthesis and release of neostriatal DA are enhanced in rats in which d-methylamphetamine destroyed a large number of nigrostriatal DA terminals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

A comparison of the subjective and cardiovascular effects of cocaine and procaine in humans.

Four normal adult volunteers were given intravenous injections of 16, 32 and 48 mg cocaine, procaine, or saline, once daily in a balanced order. An additional dose of procaine, 96 mg, was also given. Heart rate, blood pressure, and responses on the Profile of Mood States (POMS), Addiction Research Center Inventory (ARCI), and a locally developed drug effects rating scale were measured before and periodically after drug or placebo injection. The profile of action of cocaine was significantly different from that produced by both saline and the lower doses of procaine. Although responses on the ARCI and POMS after all doses of procaine were similar to those obtained after placebo, three of the subjects identified 48 and 96 mg procaine as cocaine, and rated these two drugs similarly at the higher procaine doses.

Adult↗
PubMed1983

A comparison of the subjective and cardiovascular effects of cocaine and lidocaine in humans.

Four normal adult volunteers were given intravenous injections of 16, 32 and 48 mg cocaine, lidocaine, or saline, once daily. Heart rate, blood pressure and responses on the Profile of Mood States, Addiction Research Center Inventory, and a locally developed drug effects questionnaire were measured periodically before and after drug or placebo injection. The profile of action of cocaine was significantly different from that produced by lidocaine or placebo whereas the effects of lidocaine were indistinguishable from those of placebo.

Adult↗
PubMed1983

Intragastric self-administration in rhesus monkeys under limited access conditions: methodological studies.

Rhesus monkeys were trained to self-administer psychoactive drugs by the intragastric route of administration under limited access conditions and intermittent schedules of drug delivery. Under a fixed-ratio 10 schedule, pentobarbital, diazepam, and cocaine maintained self-administration in some monkeys. Responding was not maintained by d-amphetamine under these conditions. Under fixed-ratio 10 (timeout 2 min) conditions, cocaine maintained self-administration in all animals (5/5) tested, while pentobarbital maintained responding in 2/3. At doses higher than that which maintained maximal rates, responding was inversely related to dose/injection. Drug intake was relatively constant across dose/injection of cocaine, but was a direct function of dose/injection of pentobarbital and diazepam. The procedure may be useful in assessing behavioral and pharmacological variables controlling oral self-administration of drugs.

Animals↗