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Biomedical subjects

J V Brady

Publications and source records attributed to J V Brady.

At least 19 recordsLinked to original sources
PubMed1997

Effects of cocaine and quinpirole on perceptual and motor functions in baboons.

The effects of cocaine and quinpirole were studied in baboons to determine whether quinpirole, a relatively selective D2/D3 dopamine agonist, produced effects similar to those of cocaine on perceptual and motor processes. To measure perceptual and motor function, three baboons were trained to discriminate differences between a standard vowel and four other synthetic vowels: response accuracy as well as response latencies, or "reaction times", were measured following drug administrations. Cocaine reduced reaction times in two baboons, and did not affect reaction times in a third; on the other hand, quinpirole lengthened reaction times in a dose-dependent manner in all baboons. Cocaine and quinpirole also differed in the time course to produce the maximal reaction time effect following drug administration. Cocaine and quinpirole did not differ consistently in their perceptual effects, as indicated by similar changes in d', a signal-detection index of discriminability. These distinct profiles of effects for cocaine and quinpirole suggest differing neurochemical actions for these two drugs.

Animals↗
PubMed1996

Cocaine's effects on speech sound identification and reaction times in baboons.

The effects of cocaine on speech sound discriminations was examined to determine whether cocaine's previously demonstrated effect in reducing speech sound discriminability was dependent upon either the type of stimuli employed (simple tones versus complex speech) or the procedure (stimulus detection versus stimulus discrimination). Because of demonstrated similarities in the way that baboons and humans discriminate speech, and in the way the CNS is thought to encode and process speech sounds in these two species, baboons were trained to perform a choice procedure to identify the occurrence of different synthetic vowel sounds (see text). Animals held down a lever and released the lever only when one of four target vowels sounded, and not when a fifth, standard vowel sounded. Acute IM administration of cocaine (0.0032-1.0 mg/kg) produced dose-dependent decreases in vowel discriminability that were mostly due to elevations in false alarms (i.e., releases to the standard vowel) following cocaine. Cocaine also shortened reaction times to the stimuli in two of three baboons, but to a much lesser extent than observed previously. These results suggest that cocaine may interfere with the ability of the CNS to process the acoustic cues in speech sounds, and that the effects of cocaine on reaction times may depend upon the complexity of the reaction time procedure employed.

Animals↗
PubMed1996

Patient retention in mobile and fixed-site methadone maintenance treatment.

The retention of patients (n = 399) enrolled in mobile health services (MHS), a Baltimore outpatient mobile methadone treatment program, was compared to patient retention (n = 1588) in six Baltimore fixed-site programs. Mobile program patients were retained for a median of 15.53 months in treatment in comparison to 3.90 for fixed-site patients (n = 664) from the MHS served zip codes (MHSZIPS) and 6.27 for fixed-site patients (n = 924) from zip codes other than those served by MHS (OTHERZIPS), (P < 0.001). Using Cox regression, the characteristics of patients associated with earlier discharge were (1) higher number of arrests, (2) more frequent cocaine use and (3) lower family income. These predictors of shorter retention were generally more prevalent among patients from the MHS served zip codes. Therefore, the longer retention in treatment of MHS patients as compared to OTHERZIPS fixed-site program patients is even more striking. Consistent with these differences in retention, were finding in a prior study suggesting that the mobile program provided greater access to services in reducing patient transportation cost and travel time. Thus, mobile methadone maintenance treatment appears to be a useful means of providing services.

Adult↗
PubMed1995

Cocaine's effects on speech sound discriminations and reaction times in baboons.

Three adult baboons were trained using a psychophysical procedure to discriminate between different synthetic vowel sounds [symbol: see text]. Baboons pressed and held a lever down to produce a pulsed train of a single reference vowel that served as the standard stimulus. Animals were trained to release the lever only when this standard vowel sound changed to one of the four remaining comparison vowels. A lever release within 1.5 s of this change in vowel sounds was defined as a correct detection of the change from the standard vowel to one of the comparison vowels, and was reinforced. All baboons readily learned the vowel discriminations and detected vowel changes at the 90-100% correct performance level. Acute IM administration of cocaine prior to test sessions (0.00032-3.2 mg/kg) produced dose-dependent decrements in vowel discriminability. At the same time, cocaine shortened lever release latencies (reaction times) to the vowel stimuli in two of three baboons. The cocaine-induced decrements in vowel discriminability were correlated with the degree to which frequency differences occurred among the different vowels in that lower vowel discriminability scores were found for those vowels with smaller spectral differences from the standard vowel. Further, false alarm rates were not systematically affected by cocaine, indicating that the cocaine-induced decrements in vowel discrimination accuracy occurred in the absence of systematic changes in the reliability of the baboons' discrimination performances.

Acoustic Stimulation↗
PubMed1993

Effects of cocaine on sensory motor function in baboons.

The effects of cocaine on auditory and visual threshold functions and reaction times were studied in baboons. Single IM injections of cocaine HCl (0.001-1.0 mg/kg) were administered once or twice weekly and were followed immediately by psychophysical tests designed to assess cocaine's effects on sensory thresholds and reaction times. Consistent reductions in reaction times were observed in the cocaine dose range of 0.032-0.32 mg/kg. Reaction times were decreased by 5-8% at the more effective cocaine doses. Concurrently measured auditory and visual threshold sensitivities showed no systematic changes at any of the cocaine doses studied.

Animals↗
PubMed1993

Behavior analysis applications and interdisciplinary research strategies.

The emergence of behavioral pharmacology as a basic and applied science owes its origin and development to the interactive methodological-conceptual advances that have characterized interdisciplinary research initiatives over the past half century. The resulting enhancement of academic training and research opportunities has broadened the application of behavior analysis principles to a range of clinical, educational, and industrial settings. The extent of this applied behavioral science outreach is unconstrained even by the challenges of inhospitable terrestial and extraterrestial environments.

Animals↗
PubMed1992

Acute ethanol effects on sensory/motor function in baboons with a history of chronic ethanol ingestion.

Baboons with a history of chronic, daily ethanol ingestion were subsequently studied under conditions that assessed the effects of acute oral self-administration of ethanol on auditory and visual threshold functions and reaction times. During the post-chronic experiment reported herein, the animals consumed specific amounts of ethanol twice weekly (0.1, 0.32, 1.0 or 1.3 g/kg), following which they immediately performed psychophysical tests designed to assess ethanol's effects on sensory thresholds and reaction times. Clear, dose-related increases in reaction times were observed following ethanol doses greater than 0.32 g/kg. Trends within individual threshold functions were consistent with systematic changes in auditory and visual threshold sensitivities of 1-3 dB at the high ethanol doses. Reaction time increases ranged from 25 to 180 ms above baseline levels at the highest dose (a 15% average increase). These general findings however, were in contrast to data obtained in the same animals under conditions of daily, chronic ethanol administration which characteristically showed greater sensory/motor effects of up to twice the magnitude of those observed with single doses.

Alcohol Drinking↗
PubMed1992

Zolpidem behavioral pharmacology in baboons: self-injection, discrimination, tolerance and withdrawal.

This study examined in baboons various behavioral effects of zolpidem, a short-acting imidazopyridine hypnotic which has selectivity for subtypes of the benzodiazepine receptor. Intravenous drug self-injection was studied under a fixed-ratio 80- or 160-response schedule with a 3-hr timeout after each injection. Maximal rates of self-injection maintained by zolpidem (0.01-1 mg/kg) were consistently higher than those maintained by vehicle and the benzodiazepine hypnotic triazolam. Substitution of vehicle after about 2 weeks of zolpidem self-injection (7-8 mg/kg/day) resulted in a time-limited suppression of food pellet intake, indicating a drug withdrawal effect. In a drug discrimination study, baboons were trained to discriminate either lorazepam (1.8 mg/kg p.o.) or pentobarbital (10 mg/kg p.o.) from the no-drug condition. Zolpidem (0.1-18 mg/kg p.o.) occasioned both lorazepam- and pentobarbital-appropriate responding (greater than 80%) in a dose-dependent manner. In a final experiment, zolpidem (3.2 or 5.6 mg/kg i.m.) produced ataxia and sedation that progressively decreased over 7 consecutive days of administration. The withdrawal, discriminative stimulus effects and tolerance shown with zolpidem were similar to those shown previously with benzodiazepines under similar conditions. The rates of self-injection of zolpidem were similar to those maintained by intermediate duration barbiturates (e.g., pentobarbital) and higher than those maintained by 11 benzodiazepines studied previously under similar conditions. Further research on the reinforcing effects of zolpidem may provide useful insights into mechanisms underlying the maintenance of behavior by compounds acting through the benzodiazepine receptor.

Animals↗
PubMed1991

Self-injection of barbiturates, benzodiazepines and other sedative-anxiolytics in baboons.

Self-injection of 12 sedative-anxiolytics was examined in baboons. Intravenous injections and initiation of a 3-h time-out were dependent upon completion of a fixed-ratio schedule requirement, permitting eight injections per day. Before testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. At some doses, all five of the benzodiazepines examined (alprazolam, bromazepam, chlordiazepoxide, lorazepam, triazolam) maintained rates (number of injections per day) of drug self-injection above vehicle control in each of the baboons tested. Maximum rates of benzodiazepine self-injection were generally submaximal. Of the benzodiazepines examined, triazolam maintained the highest rates of self-injection. Among the three barbiturates tested, methohexital generally maintained high rates of self-injection in contrast to hexobarbital and phenobarbital, which only maintained low rates. Of the four non-benzodiazepine non-barbiturate sedatives examined, both chloral hydrate and methyprylon occasionally maintained high rates of self-injection. Although there were differences within and across animals, baclofen maintained intermediate rates of self-injection. The novel anxiolytic buspirone maintained only low rates of self-injection that were not different from vehicle. This study further validates the self-injection methodology for assessing sedative-anxiolytic abuse liability and provides new information about drug elimination rate as a determinant of drug self-administration.

Animals↗
PubMed1991

Animal models for assessing drugs of abuse.

A major toxic effect that has limited the clinical usefulness of medicinal drugs has been their susceptibility to nonmedical use and abuse by significant segments of the population. Major research efforts have been directed toward the development of safer and more effective therapeutic agents that would not be subject to such misuse, and laboratory animal assessment models have contributed importantly to the evaluation of such compounds. There are now several converging lines of evidence that testify to the reliability and broad generality of observations concerning drug abuse liability in humans based upon such animal laboratory models. The most important point of contact that characterizes the interaction between such animal assessment models and the human drug abuse arena is the demonstrated relationship between the biochemical/pharmacological/toxic properties of drugs on the one hand, and their environmental/behavioral stimulus functions on the other. As a result of these developments in animal model research technology and the consequent advances in knowledge of drug action, an operational basis has been provided for redefining the bewildering range of phenomena and experiential pseudo-phenomena loosely identify with such terms as "addition," "dependence" and "abuse."

Animals↗
PubMed1991

Rat AA-26: behavioral pharmacology science pioneer.

Rat AA-26, despite 1950s "state of the art," nonetheless generated the first set of behavioral pharmacology cumulative records to appear in the weekly journal Science, the century-old publication of the American Association for the Advancement of Science. The laboratory exploits of this dedicated animal called early attention to the methodological fruits of a marriage between pharmacology and the experimental analysis of behavior.

Amphetamine↗
PubMed1991

Response patterns and cardiovascular effects during response sequence acquisition by humans.

The effects of temporal delays imposed between successive responses and of vitamin C administration were examined on the acquisition of response sequences and on cardiovascular reactivity during sequence acquisition. Thirteen adult subjects (6 female, 7 male), in good health, gave written consent prior to participating in 12 weekly 45-min sessions. Points, exchanged for money after each session, were presented when subjects completed 15-response sequences on a touch-sensitive three-response keypad. A position counter increased from 0 to 14 as subjects emitted correct responses in the sequence. Four novel 15-response sequences were presented each session. No delays were imposed between successive responses during the acquisition of one sequence; delays were imposed immediately following each response during the acquisition of a second sequence, thereby delaying response feedback; delays were imposed following feedback during acquisition of a third sequence, resulting in the removal of the stimulus correlated with sequence position; and, as a control condition, delays were imposed following feedback, but stimuli correlated with sequence position were reinstated prior to the next response during acquisition of a fourth sequence. Subjects were exposed to one of two delay durations (0.2 and 0.5 or 0.5 and 1.0 s) each session, and delay durations alternated every session. During Weeks 5 to 8, subjects received 3 grams of vitamin C per day, whereas during Weeks 1 to 4 and 9 to 12, subjects received placebo under single-blind conditions. All subjects acquired the sequences, as evidenced by decreasing percentages of incorrect responses across trials. When temporal delays were imposed between successive responses during sequence acquisition, acquisition efficiency was enhanced. Examination of response latencies suggested that the status of preceding responses (i.e., correct or incorrect) rather than the status of the position counter influenced subsequent responding. Cardiovascular effects were inversely related to the length of the temporal delay. Neither cardiovascular reactivity or sequence acquisition were related to vitamin C administration.

Adult↗
PubMed1990

Toward applied behavior analysis of life aloft.

This article deals with systems at multiple levels, at least from cell to organization. It also deals with learning, decision making, and other behavior at multiple levels. Technological development of a human behavioral ecosystem appropriate to space environments requires an analytic and synthetic orientation, explicitly experimental in nature, dictated by scientific and pragmatic considerations, and closely approximating procedures of established effectiveness in other areas of natural science. The conceptual basis of such an approach has its roots in environmentalism which has two main features: (1) knowledge comes from experience rather than from innate ideas, divine revelation, or other obscure sources; and (2) action is governed by consequences rather than by instinct, reason, will, beliefs, attitudes or even the currently fashionable cognitions. Without an experimentally derived data base founded upon such a functional analysis of human behavior, the overgenerality of "ecological systems" approaches render them incapable of ensuring the successful establishment of enduring space habitats. Without an experimentally derived function account of individual behavioral variability, a natural science of behavior cannot exist. And without a natural science of behavior, the social sciences will necessarily remain in their current status as disciplines of less than optimal precision or utility. Such a functional analysis of human performance should provide an operational account of behavior change in a manner similar to the way in which Darwin's approach to natural selection accounted for the evolution of phylogenetic lines (i.e., in descriptive, nonteleological terms). Similarly, as Darwin's account has subsequently been shown to be consonant with information obtained at the cellular level, so too should behavior principles ultimately prove to be in accord with an account of ontogenetic adaptation at a biochemical level. It would thus seem obvious that the most productive conceptual and methodological approaches to long-term research investments focused upon human behavior in space environments will require multidisciplinary inputs from such wide-ranging fields as molecular biology, environmental physiology, behavioral biology, architecture, sociology, and political science, among others.

Behavior↗
PubMed1990

Motivational effects of smoked marijuana: behavioral contingencies and low-probability activities.

Six adult male research volunteers, in two groups of 3 subjects each, lived in a residential laboratory for 15 days. All contact with the experimenters was through a networked computer system, and subjects' behavior was monitored continuously and recorded. During the first part of each day, they were allowed to socialize. Two cigarettes containing active marijuana (2.7% delta 9-THC) or placebo were smoked during the private work period and the period of access to social activities. Three-day contingency conditions requiring subjects to engage in a low-probability work activity (instrumental activity) in order to earn time that could be spent engaging in a high-probability work activity (contingent activity) were programmed during periods of placebo and active-marijuana smoking. During placebo administration, the contingency requirement reliably increased the amount of time that subjects spent engaged in the low-probability instrumental activity and decreased the time spent engaged in the high-probability activity. During active-marijuana administration, however, the increases in instrumental activity were consistently larger than observed under placebo conditions. The decreases in contingent activity were similar to those seen under placebo conditions. Smoking active marijuana was thus observed to produce increments in instrumental activity under motivational conditions involving contingencies for "work activities."

Adult↗