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Biomedical subjects

R R Griffiths

Publications and source records attributed to R R Griffiths.

At least 181 records · Page 10Linked to original sources
PubMed1983

Lorazepam and pentobarbital drug discrimination in baboons: cross-drug generalization and interaction with Ro 15-1788.

Four baboons were trained to discriminate lorazepam (1.0 mg/kg i.m.) and two baboons were trained to discriminate pentobarbital (5.6 mg/kg i.m.) in a two-lever drug discrimination procedure. Food delivery depended on 20 consecutive responses on one lever in sessions preceded by an injection of the training drug and on 20 consecutive responses on the other lever after no drug. All baboons reliably completed 100% of the response runs on the appropriate lever in training sessions. Test sessions were conducted in which a drug dose different from the training dose was injected and 20 consecutive responses on either lever produced food. Drug lever responding occurred after a range of lorazepam and diazepam doses in both lorazepam- and pentobarbital-trained baboons. Drug lever responding also occurred after a range of doses of pentobarbital in the pentobarbital-trained baboons but in only one of the four lorazepam-trained baboons. Ro 15-1788 (0.1-1.0 mg/kg p.o.) antagonized the effect of lorazepam but had no effect on the pentobarbital discriminative stimulus. The asymmetrical generalization with lorazepam and pentobarbital suggests a specificity of discriminative stimulus effects that heretofore have not been documented in drug discrimination experiments with benzodiazepines and barbiturates. The selective antagonism of lorazepam by the benzodiazepine-receptor antagonist Ro 15-1788 suggests that the lorazepam but not the pentobarbital discriminative stimulus is mediated at the benzodiazepine receptor.

Animals↗
PubMed1982

Precipitated withdrawal by a benzodiazepine receptor antagonist (Ro 15-1788) after 7 days of diazepam.

Baboons implanted with intragastric catheters were given diazepam (10 milligrams per kilogram of body weight) twice daily for 45 consecutive days. On days 7 and 35, they were given intramuscular injections of the benzodiazepine receptor antagonist Ro 15-1788. Mild and intermediate withdrawal signs, including retching and vomiting, were observed after 7 days of diazepam, and more frequent and intense withdrawal signs, including tremor and convulsion, occurred after 35 days of diazepam. With the termination of the diazepam injections after 45 days, a mild to intermediate withdrawal syndrome was observed over the next 15-day period.

Animals↗
PubMed1982

Differential control of puff duration and interpuff interval in cigarette smokers.

While subjects smoked cigarettes under naturalistic conditions, the duration of each puff progressively decreased as the cigarette was consumed, while the time between successive puffs progressively increased. Evidence obtained using modified half-length cigarettes indicates that puff duration, but not interpuff interval, is controlled by the distance from the burning tip (combustion zone) of the cigarette to the smoker's mouth. The results demonstrate that these two fundamental descriptors of cigarette smoking behavior are under differential control, and provide new insights into the pharmacological and behavioral variables that control cigarette smoking.

Adult↗
PubMed1982

A tethering system for intravenous and intragastric drug administration in the baboon.

A system for minimally restraining adult baboons with chronic intravenous (IV) or intragastric (IG) catheters for long term pharmacological and behavioral studies is described. The system consists of an adjustable foam-padded backplate and harness which is custom-fitted to each animal. A flexible stainless-steel cable connects the backplate to a liquid swivel through which the drugs are administered. Methods for the preparation and surgical implantation of IV and IG catheters are also described. Intravenous catheters were sequentially implanted in the internal jugular, femoral, axillary and external jugular veins. Catheters have remained patent for as long as 45 months, and catheter life appears to be conjointly determined by both site and number of successive implantations. The advantages of the harness/tether system over previously used chair-restraint procedures include greater freedom of movement, fewer restraint-related health problems, and longer experimental life of the animals.

Administration, Oral↗
PubMed1982

Smoking behavior and tobacco smoke intake: response of smokers to shortened cigarettes.

The response of four cigarette smokers to full-length and three different types of half-length cigarettes was examined in a naturalistic laboratory environment. During daily 100-min sessions, subjects smoked ad libitum: (1)full-length (100 mm) cigarettes, (2)the distal half of cigarettes, (3)the proximal half of cigarettes, or (4)the proximal half of previously smoked cigarettes. As a group, subjects smoked 75% more half-length cigarettes than full-length cigarettes. Subjects also puffed at a higher rate (i.e., had shorter interpuff intervals) on half-length than on full-length cigarettes. Mean puff duration (sec/puff) was higher when subjects smoked the distal-half cigarettes than when they smoked the proximal-half cigarettes and subjects spent proportionately more time puffing on the distal-half cigarettes than on the other three types. Through a combination of smoking more half-length cigarettes and modifying the way they smoked half-length cigarettes, subjects maintained the same intake of smoke (as measured by expired air carbon monoxide) during sessions as when they smoked full-length cigarettes. These results demonstrate that smokers make complex adjustments in their smoking behavior in response to changes in cigarette length.

Behavior↗
PubMed1982

Human cigarette smoking: manipulation of number of puffs per bout, interbout interval and nicotine dose.

In a residential research ward, cigarette smoking was studied during 12-hr daily sessions in seven volunteer human subjects with histories of regular smoking. Puff-to-puff delivery of cigarette smoke was held relatively constant by instructing and monitoring subjects in taking uniform puffs and by specifying and timing the duration of holding the smoke in the lungs (5 sec) and the duration of the interpuff interval (25 sec). When a modest response requirement of riding a stationary exercise bicycle for 1 min was required before each smoking bout consisting of eight uniform puffs, stable patterns of smoking emerged in which smoking bouts were evenly spaced within and across sessions. When the number of puffs per bout was experimentally manipulated both across and within sessions, increases in puffs ber bout resulted in increases in interbout intervals. When the interbout interval was experimentally manipulated both across and within sessions and the number of puffs per bout was free to vary, increases in interbout interval resulted in increases in puffs per bout. When both nicotine dose (0.2-1.6 mg per cigarette) and puffs per bout were varied across sessions in the same experiment, changes occurred in interbout interval in response to manipulation of puffs per bout but not nicotine dose. Although nicotine dose did not influence interbout interval or puffs per hour, subject ratings of cigarette strength tended to increase with dose.

Adult↗
PubMed1982

Experimental analysis of human cigarette smoking behavior.

A laboratory preparation has been developed that permits relatively unobtrusive measurement of naturalistic cigarette smoking behavior in humans. A series of studies is described in which volunteer subjects participated in daily sessions lasting up to 3 h. The first study showed that the intervals between consecutive cigarettes were relatively stable, both within and across sessions. An analysis of puffing for a single cigarette revealed that as the cigarette was smoked, interpuff intervals tended to become longer while puff durations became progressively shorter. The second study showed that cigarette deprivation increased the tendency for subsequent smoking as reflected in latency to smoke and number of cigarettes and puffs. In the third study no change in smoking behavior was detected when subjects were informed that they would subsequently be exposed to a period of cigarette deprivation. The final study demonstrated the responsiveness of cigarette smoking to a form of dose manipulation: decreasing the concentration of tobacco smoke delivered by using ventilated cigarette holders produced increases in the rate of puffing and total numbers of puffs. These studies demonstrate the sensitivity of this preparations and suggest that is may be valuable for exploring a range of pharmacological and behavioral variables that control human cigarette smoking.

Adolescent↗
PubMed1981

Self-injection of barbiturates and benzodiazepines in baboons.

Self-injection of three barbiturates, six benzodiazepines, and chlorpromazine was examined in baboons. Intravenous injections of drug were dependent upon completion of 160 lever presses (a 160-response fixed-ratio schedule). A 3-h time-out period followed each injection, permitting a maximum of eight injections per day. Prior to testing each dose of drug, self-injection performance was established with cocaine. Subsequently, a test dose was substituted for cocaine. Amobarbital, pentobarbital, and secobarbital maintained the highest levels of self-injection, which were similar to those maintained by cocaine. Clonazepam, clorazepate, diazepam, flurazepam, medazepam, and midazolam maintained relatively modest levels of self-injection, while chlorpromazine maintained only low levels, which were in the range of vehicle control. Of the six benzodiazepines, midazolam produced the highest levels of self-injection. At the highest self-injected doses, the barbiturates produced anesthesia in contrast to the benzodiazepines, which produced only sedation. None of the drugs affected food intake except for chlorpromazine, which produced dose-related decreases. The differences among the drug classes (i.e., barbiturate, benzodiazepine, phenothiazine) with respect to the maintenance of self-injection correspond well with the results of previous animal and human drug self-administration studies.

Animals↗
PubMed1981

Human social conversation: effects of ethanol, secobarbital and chlorpromazine.

Effects of oral ethanol, secobarbital and chlorpromazine on human vocalization were studied in a dyadic social situation using repeated observations within subject pairs. Throat microphones and voice operated relays were used to measure quantitative aspects of vocalization (conversational speech) during daily experimental sessions. Ethanol (1-6 oz of 95-proof) and secobarbital (30-300 mg) produced dose-related increases in vocalization by the subject who received active drug, while vocalization by the partner who received placebo only was not generally altered systematically. Chlorpromazine (25-100 mg) produced dose-related decreases in amount of vocalization by the subject and vocalization by partners tended to decrease as well on days when the subject received active drug. Selected scales from the Addiction Research Center Inventory were administered following social sessions to assess subjective drug effects. No consistent changes on ARCI scales were obtained after ethanol or secobarbital, while chlorpromazine produced dose-related increases on the PCAG scale. Overall, quantitative measures of vocalization in a social context provided a reliable and sensitive indicator of dose-related drug effects.

Adolescent↗
PubMed1981

Diazepam use among methadone maintenance patients: patterns and dosages.

Methadone maintenance patients who use benzodiazepine drugs were interviewed about the dosage levels, patterns, frequency and motives for their use of these drugs. The sample was drawn from two treatment clinics, one in Baltimore (N = 12) and one in Philadelphia (N = 17). Benzodiazepine use was prevalent at both of these clinics - 65 -70% of maintenance patients had positive urinalysis tests during a single month. Ninety-three per cent of survey participants identified diazepam as the drug which they used most often. The median value of the usual daily dose was 40 - 45 mg; 31% reported usual daily doses between 70 and 300 mg and 62% had experience with doses of 100 mg and higher. The majority of the sample reported taking diazepam in a single daily dose within one hour of the time that they ingested their daily methadone; 72% of the sample indicated that diazepam boosts the effects obtained from the daily methadone dose. Another sample of addicts who reported extensive experience with both benzodiazepines and barbiturates indicated that diazepam increases the effects of methadone while barbiturates produce no change in the effects of methadone. Results of this study suggest that patterns and dosages of diazepam use among methadone maintenance patients are primarily abusive rather than therapeutic.

Adult↗
PubMed1981

Cigarette smoking and subjective response: effects of d-amphetamine.

The effects of oral d-amphetamine on cigarette smoking and subjective responses were determined in eight adults who smoked cigarettes. Subjects were tested each day in rooms that provided a comfortable, natural environment while cigarette-smoking behavior was automatically monitored. Each subject served as his own control and was tested at four d-amphetamine dose levels (0, 5, 15, 25 mg) that were scheduled according to five randomized block sequences. d-Amphetamine induced dose-related increases in the number of cigarettes smoked. total puffs, weight of tobacco consumed, expired air carbon monoxide levels, subject-related satisfaction derived from smoking, and scores on scales of the Addiction Research Center Inventory (ARCI). As measures of drug effects, both the behavioral measures of smoking and the ARCI scales were sensitive when the data from the subjects were grouped and tested for statistical significance. Behavioral measures, however, were more sensitive than the ARCI scales when a within-subject analysis was performed.

Adult↗
PubMed1981

Choice between food and heroin: effects of morphine, naloxone, and secobarbital.

Baboons responded on a choice task on which discrete trials involved choosing between an intravenous injection of heroin (.32 or 1.0 mg/kg) or the availability of food pellets. An intertrial interval of three hours followed the completion of each trial. Under baseline conditions baboons consistently completed the eight available trials each day. Typically, animals chose heroin on three or four trials a day and food on the remaining trials. Animals tended to space the selection of heroin rather than choosing heroin on consecutive trials. A series of single-day experimental manipulations was undertaken to characterize performance further. Manipulation of the heroin dose produced shifts in the relative frequency of choosing the drug option which were inversely related to dose. Manipulation of number of pellets per food trial produced little change in distribution of choices. Noncontingent administration of morphine produced dose-related decreases in relative frequency of heroin choices, and a higher dose decreased the number of trials completed. Noncontingent naloxone produced dose-related increases in the relative frequency of heroin choices. Noncontingent secobarbital had no effect on distribution of choices, and high doses reduced the number of trials completed per day. The results suggest that morphine and naloxone produce shifts in this choice behavior by selectively interacting with the reinforcing properties of the option involving heroin.

Animals↗