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Biomedical subjects

L D Byrd

Publications and source records attributed to L D Byrd.

At least 19 recordsLinked to original sources
PubMed1992

A method for quantitating motor deficits in a nonhuman primate following MPTP-induced hemiparkinsonism and co-grafting.

This report describes a nonhuman primate model of MPTP-induced hemiparkinsonism and the recovery of motor function following co-grafting of adrenal medullary tissue and peripheral nerve into the lesioned area of the brain. A rhesus monkey (Macaca mulatta) trained to perform a complex, discrete-trial, operant task served as the subject. After behavioral performance on the task had stabilized and a high level of accuracy was maintained, 0.4 mg/kg MPTP was infused acutely via the left carotid artery to produce a marked impairment of movement of the right arm. Eighteen weeks later, medullary tissue from the left adrenal gland was grafted along with peripheral nerve into the left caudate nucleus. During the original baseline training condition, right- and left-hand performances were comparable on all dependent measures. However, right-hand performance was severely impaired following unilateral MPTP treatment, and left-hand performance was unaffected. Right-hand performance recovered only after adrenal medullary tissue was transplanted with peripheral nerve into the brain. Neuroanatomical analysis of brain tissue showed the anticipated neuronal loss in the left substantia nigra due to MPTP administration and evidence of adrenal medullary cell survival in the area of the co-graft. The data demonstrate that the rhesus monkey and the behavioral task developed during this study can be efficacious in characterizing the effects of MPTP on psychomotor function and in assessing the outcome of new strategies for treating Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

Enhanced sensitivity to the behavioral effects of cocaine after chronic administration of D2-selective dopamine antagonists in the squirrel monkey.

The behavioral effects of cocaine (0.03-3.0 mg/kg i.v.) were determined in squirrel monkeys (Saimiri sciureus) trained to respond under a fixed-interval 300-sec schedule of stimulus termination. A session consisted of 13 consecutive fixed-interval components, each followed by a 60-sec timeout. Graded doses of cocaine were injected during selected timeout periods using a cumulative-dosing procedure. Subsequently, two dopamine D2-selective antagonists, spiperone and raclopride, and a D1-selective antagonist, SCH 23390, were administered chronically for a 2-week period. Due to pronounced time course differences, raclopride and SCH 23390 were infused continuously via osmotic minipump, and spiperone was administered i.m. twice per week. Spiperone and raclopride markedly suppressed responding during the 2-week period. When the effects of cocaine were redetermined 3 days after spiperone or 1 day after raclopride administration was terminated, there was a parallel leftward shift in the dose-effect curve, indicating enhanced sensitivity to cocaine. Three days later, sensitivity to cocaine had changed and was similar to that obtained before chronic drug administration. In contrast, SCH 23390 did not alter sensitivity to cocaine after chronic administration was terminated, even though it did attenuate the behavioral effects of cocaine as effectively as spiperone and raclopride. Chronic administration of spiperone did not alter sensitivity to nisoxetine, a norepinephrine uptake inhibitor, or quipazine, a serotonin agonist. The acute administration of spiperone in combination with cocaine also differed markedly from nisoxetine and quipazine. The pronounced rate-decreasing effect of spiperone was attenuated by cocaine in a dose-dependent manner, but not by nisoxetine or quipazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Characterization of the effects of cocaine and GBR 12909, a dopamine uptake inhibitor, on behavior in the squirrel monkey.

The behavioral effects of cocaine and GBR 12909, a highly selective dopamine uptake inhibitor, were compared in squirrel monkeys trained to respond under a fixed-interval schedule of stimulus termination and a second-order schedule of drug self-administration. Both drugs exhibited similar pharmacological profiles; intermediate doses increased response rates markedly and higher doses decreased response rates below control values. The magnitude of the rate-increasing effect was similar for cocaine and GBR 12909, although cocaine was approximately 3 times more potent. In contrast, the direct-acting dopamine agonists, SKF 38393 and quinpirole, produced only decreases in response rates. When cocaine and GBR 12909 were studied in combination with dopamine antagonists, the effects of either on fixed-interval performance were attenuated in a similar manner by a D1-selective antagonist (SCH 23390) and a D2-selective antagonist (spiperone), indicating the involvement of both D1 and D2 receptor subtypes. In contrast, an alpha 1-selective antagonist (prazosin) did not alter the dose-effect curve for cocaine or GBR 12909 in a manner that indicated a pharmacological antagonism. When doses of cocaine were administered in combination with GBR 12909, the effects on behavior were additive. However, the combined effects of cocaine and SKF 38393 or cocaine and quinpirole were more complex and did not appear to be additive. When the cocaine or GBR 12909 was self-administered under a second-order, fixed-interval schedule of drug injection, schedule-appropriate responding was maintained and the potency difference between the two drugs was comparable to that observed under the stimulus-termination schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Effects of dominance rank on d-amphetamine-induced increases in aggression.

Previous research has suggested that certain social factors, e.g., dominance rank, can determine the behavioral effects of drugs in individual members of a social group. In the present experiment, the effects of d-amphetamine were studied in two adult male monkeys with dominance rankings that changed during a reorganization of the social hierarchy in a captive group of stumptail macaques (Macaca arctoides). A range of doses of d-amphetamine was administered to each subject, and dose-effect curves were determined before and after group reorganization and stabilization. The data revealed drug effects which were dependent upon dose and the social rank of the animals. When either subject occupied the highest ranking or alpha position within the dominance hierarchy, rate of aggressive behavior initiated by the subject was several times greater than when that monkey occupied a lower position within the dominance hierarchy. Moreover, for either subject, the dose-effect curve was shifted to the right when the monkey was highest in the dominance hierarchy. Finally, aggression initiated by the drug-treated subject was directed more frequently toward adult members of the group when the subject was highest in the hierarchy and toward nonadult animals when the subject was lower in the hierarchy. These data support the hypothesis that the dominance position of an animal in a group can be a determinant of the behavioral effect of certain drugs.

Aggression↗
PubMed1988

Differential effects of cocaine and pentobarbital on fixed-interval and random-interval performance.

Reports have indicated that the behavioral effects of a drug can be related to the nondrug control rate of behavior in the absence of the drug. To investigate the purported relationship between control rate and drug rate, squirrel monkeys were trained under a fixed-interval 300-s schedule of stimulus-shock termination, a procedure that engendered a wide range of response rates. A light illuminated the experimental chamber during the fixed interval, and the first lever press after 300 s had elapsed terminated the light for 30 s and precluded an electrical stimulus to the tail. Following acute intramuscular administration of cocaine (0.03-0.56 mg/kg), overall rate increased and different control rates of responding, during different parts of the fixed interval, converged toward a common rate. Subsequently, the schedule was changed to a multiple fixed-interval 300-s random-interval 300-s schedule; performance during the random-interval component was characterized by steady responding at a uniformly high rate. Analysis of fixed-interval and random-interval performances following acute cocaine administration revealed convergence of response rates toward a common, uniform rate. Pentobarbital (0.3-10.0 mg/kg) only decreased overall rate, and different control rates of responding during the fixed interval did not converge toward a common rate. The results indicate that this type of analysis can be useful in comparing pharmacological agents from different classes and that the rate at which responding becomes uniform can provide a quantitative behavioral end point for characterizing drug effects on behavior.

Animals↗
PubMed1987

Behavioral effects of phencyclidine and ketamine alone and in combination with other drugs.

The behavioral effects of phencyclidine (PCP) and ketamine administered alone and in combination with naloxone, atropine, methyl atropine, chlorpromazine and d-amphetamine were studied in squirrel monkeys trained to press a response lever under a fixed-ratio 30 schedule maintained by the termination of a stimulus associated with electric shock presentation. Under non-drug conditions, a period of high-rate responding in the presence of the stimulus associated with shock presentation was followed by a period of no responding during a 40-s timeout scheduled between fixed-ratio components. Mean rates of responding during fixed-ratio components decreased monotonically as PCP dose increased from 0.1 to 0.56 mg/kg, and doses of 3.0 and 5.6 mg/kg ketamine produced decreases in mean response rate comparable to doses of 0.3 and 0.56 mg/kg PCP. The dose-effect functions revealed that ketamine was approximately one-tenth as potent as PCP. The present data also characterized the time-course effects of PCP and ketamine, with the former having effects that were slower in onset yet more persistent in time. None of the drugs studied in combination with PCP and ketamine provided evidence of a pharmacological antagonism of the behavioral effects of the latter two drugs. Rather, the data indicated an enhancement of behavioral effects when certain drug combinations were studied.

Animals↗
PubMed1987

Extracellular dopamine in rat striatum following uptake inhibition by cocaine, nomifensine and benztropine.

A microdialysis/smallbore chromatographic system was used to monitor changes in extracellular dopamine concentration in the striatum of the rat following administration of drugs that block catecholamine uptake. Analysis of 0.5 microliter of dialysate every 5 min showed dose-dependent elevations in extracellular dopamine following systemic administration of nomifensine (1 and 10 mg/kg), benztropine (5 and 25 mg/kg) and cocaine (3, 10 and 30 mg/kg). The order of potency in vivo was nomifensine greater than cocaine greater than benztropine. The short sampling interval allows accurate temporal profiles following pharmacological manipulations to be acquired.

Animals↗
PubMed1987

Effects of phencyclidine and ketamine on cardiovascular activity and temperature in the squirrel monkey.

Heart rate (HR), mean arterial blood pressure (BP) and core temperature (TEMP) were recorded from chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous (i.v.) injections of phencyclidine and ketamine and intramuscular (i.m.) injections of ketamine. Phencyclidine (0.03-3.0 mg/kg) and ketamine (0.3-30.0 mg/kg) i.v. increased BP and decreased TEMP, and the changes in BP and in TEMP were greater in magnitude and duration after phencyclidine. Heart rate also increased monotonically after 0.03-0.3 mg/kg phencyclidine or 0.3-10.0 mg/kg ketamine, but the effects of higher doses of either drug were biphasic with decreases followed by increases in HR. When either of two doses of ketamine (10.0 and 30.0 mg/kg) was injected i.m., the effects were qualitatively similar to those observed after i.v. administration although of much less magnitude, and there was no evidence of a biphasic change in HR. The data show that these two dissociative anesthetics differ in duration of action and in magnitude of effect on cardiovascular activity and core temperature in the squirrel monkey, and that phencyclidine is approximately ten times as potent as ketamine.

Animals↗
PubMed1986

Effects of d-amphetamine on grooming and proximity in stumptail macaques: differential effects on social bonds.

An experiment was conducted to determine the effects of d-amphetamine on the expression of certain social behaviors, i.e., grooming and proximity, initiated by adult male stumptail macaques living in a large group comprised of both sexes and all ages. Traditionally, grooming behavior and proximity behavior have been considered indicators of social affinity. Under the non-drug conditions of the present study, the two types of behaviors were initiated in greatly different proportions toward individual members of the group. The acute administration of d-amphetamine (0.01-0.3 mg/kg IM) resulted in marked increases in the rate of self-grooming, i.e., the number of self-grooming bouts initiated per hour, for all subjects and in decreases in the rate at which subjects groomed other monkeys, but the drug appeared to have no effect on the rate at which a subject positioned itself near another monkey (proximity). Consequently, the drug had different effects on the two relationships represented by grooming behavior and proximity behavior. Drug administration also produced changes in the distribution of grooming and proximity initiated by the subjects toward various classes of interactants in the group. Furthermore, the changes were not of the same magnitude for the two behaviors. These data provide additional evidence that different group members receive differential behavioral interactions from drugged subjects.

Animals↗
PubMed1986

Similarities in the rate-altering effects of white noise and cocaine.

The effects of white noise and cocaine on squirrel monkeys' fixed-interval responding were compared to determine whether the presentation of an exteroceptive stimulus could produce rate-altering effects of the type typically observed following drug administration. To investigate the relationship between control response rate and response rate in the presence of drug or noise, the monkeys were trained under a fixed-interval 300-s stimulus-shock termination schedule in order to generate a wide range of local response rates. A light illuminated the experimental chamber during the interval and, after 300 s elapsed, a lever press during a 3-s period terminated the light and precluded the occurrence of a harmless electrical stimulus that otherwise was delivered at the end of the 3-s period. Each interval was followed by a 30-s timeout during which the chamber was darkened and responses had no consequences. Following intramuscular administration of cocaine, different rates of responding characteristic of control performance converged toward a common rate and, at an appropriately high dose, response rate during the fixed interval became more uniform. When white noise was presented continuously during a given session, different response rates also converged toward a common rate and, at an appropriate intensity, response rate became more uniform. Interactions were obtained when cocaine and white noise were presented together, indicating the possibility of a common behavioral mechanism of action. The results suggest that rate-altering drug effects may be, in part, a result of the ability of drugs to produce nonspecific stimulus effects similar to those observed for exteroceptive stimuli.

Acoustic Stimulation↗
PubMed1985

d-Amphetamine induced changes in social interaction patterns.

The behavioral effects of d-amphetamine were studied in a group of stumptail macaques in a large outdoor enclosure. d-Amphetamine altered characteristic patterns of aggressive and affiliative behaviors in adult males that received the drug. Each monkey that received d-amphetamine increased its aggression toward non-adult animals in the group and decreased aggression toward adult members. In subjects for which genealogy was known, d-amphetamine increased aggression toward kin-related members of the group and decreased aggression toward non-kin monkeys. The effects of the drug on affiliative behaviors were less uniform and, therefore, less conclusive. Three subjects decreased affiliation and two increased affiliation toward non-adult monkeys. The results demonstrate that d-amphetamine can alter substantially the behavior of drug-treated members of a group and, in addition, that the drug can indirectly affect specific subsets of the group even though they did not receive the drug.

Aggression↗
PubMed1984

Contrasting effects of d-amphetamine on affiliation and aggression in monkeys.

Amphetamine has been observed to alter conditioned or learned behavior in individually housed animals, as well as naturally-occurring behavior characteristic of animals living in groups. This study is concerned with the effects of d-amphetamine on affiliative and aggressive behavior in adult male stumptail macaques (Macaca arctoides) living in a large, heterogeneous social group. Using standardized observational techniques, the affiliative and aggressive behaviors initiated by five adult male monkeys were characterized and quantitated in the absence of and following drug administration. Acute administration of a range of doses of d-amphetamine (0.003-0.56 mg/kg) resulted in a monotonically depressive effect on the rate of affiliative behavior initiated by the experimental animals. In contrast, d-amphetamine increased the rate of aggressive behavior initiated by the highest- and lowest-ranking monkeys, and had little or no effect in the mid-ranking monkeys. These results show that d-amphetamine can have qualitatively different effects on affiliative and aggressive behavior in the same subjects. The results also provide evidence that the effects of d-amphetamine can be determined by the hierarchical or dominance position of the subject in the group.

Aggression↗
PubMed1983

Effects of d-amphetamine on self-aggression and posturing in stumptail macaques.

The behavioral effects of d-amphetamine sulfate were studied in adult male stumptail macaques living within a large heterogeneous group in an outdoor enclosure. Among five subjects that received a range of doses (.01 to .3 mg/kg), d-amphetamine increased self-aggressive behavior and abnormal posturing in subjects that exhibited these types of behavior prior to drug administration, but it had no effect in subjects not exhibiting those activities in the absence of the drug. For the former subjects, the dose-effect curves for self-aggression were of an inverted U-shape analogous to the effect of d-amphetamine on schedule-controlled behavior. Over the range of doses studied, the curve for abnormal posturing was monotonic. The data indicate that d-amphetamine can have effects on untrained behavior in individual animals in a quasinatural environment that are qualitatively and quantitatively similar to the behavioral effects observed in other laboratory environments, and that d-amphetamine does not evoke or increase a behavioral response in individual subjects that do not exhibit the response in the absence of the drug.

Aggression↗
PubMed1979

The behavioral effects of cocaine: rate dependency or rate constancy.

The behavioral effects of cocaine were studied in squirrel monkeys trained to press a response key under an 8-min fixed-interval (FI) schedule of electric shock presentation. Overall mean rate of responding increased at 0.03--0.3 mg/kg (i.m.) and decreased at 1.0--3.0 mg/kg. Increased responding during the initial and middle periods of the fixed-interval accounted for the increase in overall mean rate; response rate during the final two min of the interval did not increase at any dose. An analysis based on response rate during individual 1-min segments of the 8-min interval showed that the rate during the interval became more uniform, and the pattern of positively accelerated responding became more linear, as dose increased. At 0.3--1.0 mg/kg, response rate was relatively constant and independent of the control, pre-drug rate of responding.

Animals↗
PubMed1979

A tethering system for direct measurement of cardiovascular function in the caged baboon.

A device suitable for the continuous measurement of physiological activity in large, conscious monkeys has permitted the direct recording of systemic arterial blood pressure and heart rate in caged baboons. The device comprises a lightweight fiberglass backpack, retained in place on the baboon by a thoracic elastic band and shoulder straps, and a flexible stainless steel tether connecting the pack to an electrocannular slip-ring in the top center of the baboon's cage. A chronically indwelling arterial catheter inserted retrograde into the abdominal aorta via the internal iliac artery and connected to a small pressure transducer on the pack provides direct measurement of blood pressure and heart rate. Body fluids can be sampled or drugs administered via an indwelling catheter in the inferior vena cava. Electrical and fluid connections between the fiberglass pack and recording and infusion equipment located outside the cage pass through the flexible tether and remain protected from the subject. The reliability of the tethering system has been demonstrated in physiological, pharmacological, and behavioral experiments with baboons.

Animals↗