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J V Brady

Publications and source records attributed to J V Brady.

At least 19 recordsLinked to original sources
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

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↗
PubMed1990

Smoked marijuana effects on tobacco cigarette smoking behavior.

The effects of marijuana smoke exposure on several measures of tobacco cigarette smoking behavior were examined. Eight healthy adult male volunteers, who smoked both tobacco and marijuana cigarettes, participated in residential studies, lasting 10 to 15 days, designed to measure the effects of marijuana smoke exposure on a range of behavioral variables. Tobacco cigarettes were available throughout the day (9:00 A.M. until midnight). Each day was divided into a private period (9:00 A.M. to 5:00 P.M.), during which subjects were socially isolated, and a social period (5:00 P.M. to midnight), during which subjects could interact. Under blind conditions, subjects smoked placebo and active marijuana cigarettes (0%, 1.3%, 2.3%, or 2.7% delta 9-tetrahydrocannabinol) four times daily (9:45 A.M., 1:30 P.M., 5:00 P.M. and 8:30 P.M.). Each subject was exposed to both placebo and one active dose over 2- to 5-consecutive-day intervals, and dose conditions (i.e., placebo or active) alternated throughout the study. Active marijuana smoking significantly decreased the number of daily tobacco smoking bouts, increased inter-bout intervals and decreased inter-puff intervals. Marijuana decreased the number of tobacco smoking bouts by delaying the initiation of tobacco cigarette smoking immediately after marijuana smoking, whereas decreases in inter-puff intervals were unrelated to the time of marijuana smoking. No consistent interactions between marijuana effects and social or private periods (i.e., time of day) were observed.

Adult↗
PubMed1989

The regularity of smoked marijuana self-administration.

Three male research volunteers lived in a residential laboratory for 12 days in a study designed to investigate factors controlling patterns of marijuana smoking. All contact with the experimenters was through a networked computer system and subjects' behaviors were continuously recorded. During the first six hr of the day (0945-1545), subjects remained in their private rooms engaging in planned work activities, and during the remainder of the day (7 3/4 hr) they were allowed to socialize (1600-2345). Subjects were instructed that up to five active marijuana cigarettes (1.84% delta 9 w/w THC) could be smoked on designated days between 0945 and 2200. Cigarettes were available on request. Subjects requested all five cigarettes on 15 of 18 possible occasions (three subjects x six days of availability) with a mean latency to the first cigarette of 22 min. The pattern of self-administration was remarkably similar among subjects with all subjects smoking two cigarettes during the private work period and three cigarettes during the social access period. Subjects 1 and 2 smoked 90% of their social period cigarettes together in the social area, while Subject 3 smoked all of his cigarettes alone in his private room.

Adult↗
PubMed1979

Progressive ratio and fixed ratio schedules of cocaine-maintained responding in baboons.

Responding maintained under progressive ratio (PR) and fixed ratio (FR 160) schedules of IV saline or cocaine (0.01-4.0 mg/kg) injections was studied in baboons. Each injection was followed by a time-out period which was 3-h with the PR schedule and was either 3 or 12 with the FR schedule. On the PR schedule the ratio requirement was systematically increased each day until reaching the 'breaking point' at which self-injection performance fell below a criterion level (one or zero injections per day). Overall response rates on the PR schedule increased with progressive increases in the ratio until a maximum at which an abrupt reduction in responding occurred. With the 3-h time-out the dose-breaking point function on the PR schedule was similar to the dose-response rate function on the FR schedule. These dose-effect functions were inverted U-shaped curves characterized by a graded ascending limb (0.01-0.32 mg/kg) and a downturn at the highest doses (3.0-4.0 mg/kg). On the FR schedule the downturn in the dose-response rate function was attributable to a cumulative drug effect as revealed by manipulation of time-out duration and analysis of sequential interresponse time distributions and cumulative response records. PR and FR schedules provide similar information about the relative reinforcing efficacy of different cocaine doses.

Animals↗
PubMed1979

Behavioral assessment of risk-taking and psychophysical functions in the baboon.

Laboratory procedures have been developed for the experimental analysis of risk-taking and psychophysical functions in dog-faced baboons (Papio anubis). In a procedure analogous to the traffic light situation, animals are rewarded with food pellets for completing a fixed ratio of 100 responses in the presence of a green light. Superimposed upon this baseline performance are 5-second presentations of a yellow warning light terminated by a red light in the presence of which all responses are punished with electric shock. When the yellow light is introduced late in the sequence (e.g., after 93 responses have been completed), response rates increase and the 100-response ratio is completed before the 5-second yellow light times out. When the yellow light appears early in the sequence (e.g., after 73 responses) a marked decrease in response rate is observed with cessation of responding before onset of the red light. The sensitivity of components of this risk-taking performance to pharmacological toxicants is reported and psychophysical assessment of relevant sensory-motor effects described.

Animals↗