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R W Foltin

Publications and source records attributed to R W Foltin.

At least 109 records · Page 6Linked to original sources

Residential laboratory research: a multidimensional evaluation of the effects of drugs on behavior.

The data presented point to the importance of studying drug effects under conditions similar to those in which drugs are taken outside of the laboratory. Interactions between the reinforcing and other direct effects of these drugs, as well as their interactions with ongoing environmental events can only be evaluated under such conditions. These data support the utility of a residential research facility for the investigation of substance use and its effects under conditions which approximate those in which people live outside of the laboratory. This unique laboratory, designed for continuous observation of human behavior over extended periods of time, provides a controlled environment with the flexibility for establishing a range of subject behaviors, and the ability to simultaneously monitor a wide range of individual and social behavior patterns. We can study regulation of drug intake and its effects, both within a day and over days, assessing the effects of experimental manipulations on the patterning of self-administration behavior as well as the performance of a range of other behaviors as a function of drug self-administration. The design of such studies is a logical extension of basic preclinical research, as well as more traditional human behavioral pharmacology research. Although little data are yet available on drug-related "hangovers" or "morning after" effects, it should be clear that this residential laboratory would provide ideal experimental conditions for such research. We have shown that subjects will exhibit stable patterns of drug self-administration which are sensitive to systematic manipulation of variables. Therefore, we are in the position of being able to evaluate longer term effects on performance of drug-taking behavior as it occurs under conditions approximating the natural ecology. The examples of data collected in the laboratory have demonstrated that drug effects are not a unitary phenomenon, but instead depend on ongoing behaviors as well as pharmacological variables such as drug and dose. If we are going to evaluate drugs and the way in which they affect workplace behavior, we must carry out our evaluation under conditions which approximate those in which people might be using them, while at the same time controlling extraneous variables and protecting the participants from possible deleterious effects. We have shown that drugs, such as marijuana and amphetamine, have divergent effects that are influenced by both situational and behavioral factors. A thorough evaluation of the effects of any drug on behavior is, therefore, dependent on the evaluation of the drug's effects under the conditions in which it is likely to be taken.

Adult↗

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↗

Differential development of tolerance to the effects of d-amphetamine and fenfluramine on food intake in baboons.

Food intake of six adult male baboons (Papio cynocephalus anubis) was monitored during daily 22-hr experimental sessions. Food was available under a chain schedule with two components. After completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component," during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. Complete dose-response functions for amphetamine and fenfluramine were determined before, during and after a period of repeated administration of each drug. On the first day of repeated administration both drugs decreased intake during both the first 8 hr and the entire session to 65% of baseline. Total intake returned to 93% of baseline during repeated amphetamine, but only to 76% of baseline during repeated fenfluramine. There was no recovery of intake, however, during the first 8 hr of the session. Baboons given repeated amphetamine were tolerant to the food intake decreasing effects of acute amphetamine, but not acute fenfluramine. Baboons given repeated fenfluramine did not develop tolerance to the effects of fenfluramine or amphetamine on food intake. The absence of cross-tolerance or increased sensitivity between amphetamine and fenfluramine suggests that although both serotonergic and dopaminergic systems are involved in feeding, they can influence food intake independently.

Analysis of Variance↗

Effects of desipramine maintenance on cocaine self-administration by humans.

Six research volunteers with histories of cocaine use were tested in a cocaine choice paradigm to investigate the effects of desipramine maintenance on cocaine-taking behavior. Subjects were allowed to self-administer i.v. saline or cocaine (8, 16 or 32 mg) in daily 3-hr sessions to establish baseline levels of self-administration, self-reported effects of the drug and changes in heart rate and blood pressure. Each subject was then maintained on daily doses of desipramine for 3 to 4 weeks, after which a second cocaine self-administration dose-response curve was generated under desipramine maintenance. This maintenance had no effect on cocaine self-administration. There was, however, a significant increase in heart rate and blood pressure during desipramine maintenance. Desipramine maintenance also resulted in a change in the profile of cocaine's self-reported effects. In some cases (e.g., Arousal and Vigor on the Profile of Mood States, Benzedrine Group scale on the Addiction Research Center Inventory), reports of cocaine's effects were significantly reduced under conditions of desipramine maintenance, and in others (e.g., Anxiety, Anger and Confusion on the Profile of Mood States), those reports were significantly increased. Furthermore, there was a significant decrease in subjects response to an "I want cocaine" question while under desipramine maintenance. The data suggest that desipramine does not affect the reinforcing properties of cocaine, but may interfere with its other stimulus properties. Furthermore, the cardiovascular effects of desipramine appear to have the potential for toxicity when that drug is administered in combination with cocaine.

Adult↗

Food intake in baboons: effects of diazepam.

Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22 h. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component" during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. The effects of diazepam (DZP: 0.12-4.0 mg/kg) were determined by having the baboons drink a dose on Tuesdays and Fridays 45-60 min before the daily session. DZP produced dose-dependent increases in food intake in three of the four baboons. DZP increased the size of the first two meals and total duration of eating, but had no effect on eating rate or the number of meals within a session. The effect of DZP on the topography of feeding of baboons differs from previous reports on the effects of benzodiazepines on the topography of feeding in rodents. This suggests that species or procedural differences influence the effects of DZP on food intake.

Animals↗

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↗

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

Fifteen adult male research volunteers, in five groups of three subjects each, lived in a residential laboratory for up to 20 days. All contact with the experimenters was through a networked computer system, and subjects' behaviors were monitored continuously and recorded. During the first part of each day, subjects remained in their private rooms doing planned work activities, and during the remainder of each day, they were allowed to socialize. One or two cigarettes containing active marijuana (1.3-2.7% delta 9-THC) or placebo were smoked during both the private work period and the period of access to social activities. Two-or three-day contingency conditions requiring subjects to engage in a low-probability recreational activity in order to earn time that could be spent engaging in a high-probability recreational 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 contingent activity. During active marijuana administration, however, the increases in instrumental activity were consistently smaller than observed under placebo conditions. The decreases in high-probability contingent activity were similar across drug conditions. Smoking active marijuana was thus observed to produce instrumental decrements under motivational conditions involving recreational contingencies.

Adult↗

Food intake in baboons: effects of a long-acting cholecystokinin analog.

Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22h. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e. a meal, became available under the second "consumption component" during which each response produced a 1-g food pellet. After a 10-min interval in which no response occurred, the consumption component was terminated. A long-acting cholecystokinin (CCK) analog U-67827E (U-67: 0.80-3.2 micrograms/kg) was administered, in the thigh muscle, at 1100 hrs immediately prior to the start of the daily session on Tuesdays and Fridays. U-67 significantly reduced intake during the first 8-h of the session, and intake during the entire 22-h session. The decreased intake was due to a significant decrease in the size of the first meal of the session as a consequence of decreased duration of feeding without a change in response rate. U-67 also produced dose-dependent increases in latency to the first meal of up to 2.5 h. These results demonstrate that a long-acting CCK analog decreases food intake over a prolonged period of time in a naturalistic feeding situation. In addition, the effects of U-67 were limited to the consumption component, suggesting that this CCK analog affected food intake by interacting with physiological mechanisms specifically associated with feeding.

Animals↗

The effects of smoked Marijuana on interpersonal distances in small groups.

Twelve adult male research volunteers lived, in groups of three, in a residential laboratory for 7 days. During the later portion of the day (1700-2345), they had the option to socialize with or without access to video-taped films. Four cigarettes containing active marijuana (0-2.7% delta 9 THC) were smoked daily, two prior to and two during the social access period. Active marijuana decreased verbal and either increased or decreased non-verbal interaction time depending on baseline rates. Decreased verbal interactions were associated with increased interpersonal distance.

Adult↗

Effects of anorectic drugs on the topography of feeding behavior in baboons.

Food intake of six adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22 hr. Food was available under a chain schedule with two-components. After completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component" during which each response produced a 1-g food pellet. After 10 min in which no response occurred, the consumption component was terminated. When given p.o. 45 to 60 min before the start of the daily session, anorectic drugs, with the exception of (+/-)-phenylpropanolamine, produced dose-dependent decreases in food intake, with the following order of potency: phentermine greater than mazindol greater than diethylpropion greater than phendimetrazine = chlortermine = phenmetrazine = chlorphentermine. Feeding topography was differentially affected by drug administration. The latency to the first meal was increased by all of the drugs except chlorphentermine. Only diethylpropion, phendimetrazine and mazindol decreased the number of daily meals, whereas only diethylpropion, phendimetrazine, phenmetrazine and clortermine decreased the size of the first meal. Mazindol was the only anorectic drug tested that did not decrease intake during the first 8 hr of the session. (+/-)-phenylpropanolamine did not decrease food intake in the tested dose range. Phencyclidine, by decreasing intake during the first 8 hr, but not the entire 22-hr session, affected feeding topography differently than the anorectic drugs. In contrast to anorectic drug administration, decreases in food intake after phencyclidine administration were followed by caloric compensation for this initial decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of varying procurement costs on food intake in baboons.

Food intake of four adult male baboons (Papio anubis), ranging in weight from 18 to 33 kg, was monitored during daily experimental sessions lasting 22 hours. Food was available under a two-component operant schedule designed to mimic food availability in the natural ecology. The first component was a "procurement" component which consisted of pulling the manipulandum a set number of times under a fixed-ratio (FR) operant schedule. Following completion of the procurement response requirement, access to food, i.e., a meal, became available under the second "consumption" component during which each response produced a food pellet (one-gram banana-flavored pellets, 3.1 kcal/g). After a 10-minute interval in which no response occurred, the consumption component was terminated. In order to gain access to another meal, the baboon had to complete the ratio requirement of the procurement component. Increasing the ratio requirement of the procurement component from 10 to 200 had no significant effect on mean total daily intake, but significantly reduced the number of meals from 7.4 under the FR10 requirement to 3.6 under the FR200 procurement component. There were no differences among baboons in mean meal size, or intermeal-interval under each procurement requirement. Similar patterns of cumulative daily intake were observed within baboons under all ratio requirements of the procurement component, and there were few significant correlations between meal size and postmeal-interval, or premeal-interval and meal size in any baboon.

Animals↗

Food intake in baboons: effects of d-amphetamine and fenfluramine.

Food intake of four adult male baboons (Papio c. anubis) was monitored during daily experimental sessions lasting 22 hours. Food was available under a two-component operant schedule. Following completion of the first "procurement component" response requirement, access to food, i.e., a meal, became available under the second "consumption component" during which each response produced a one-g food pellet. After a 10-minute interval in which no response occurred, the consumption component was terminated. The effects of oral d-amphetamine (AMPH: 0.03-1.0 mg/kg) and fenfluramine (FEN: 0.25-2.0 mg/kg) were determined by having the baboons drink a dose on Tuesdays and Fridays 45 to 60 min before the daily session. Dose-dependent decreases in food intake were observed with AMPH being four times as potent as FEN. Although both drugs were equally efficacious in decreasing food intake, they had dissimilar effects on the topography of feeding behavior. AMPH decreased food intake by increasing the latency to the first meal, decreasing the size of the first meal, and decreasing the number of meals within a session. FEN, in contrast, had no significant effect on latency to the first meal or size of the first meal, but decreased the number of meals within a session. In addition, the drugs had different effects on the patterning of responding within the first meal. Finally, at the doses tested, there was no evidence of nonspecific motor deficits disrupting food intake. Although there are some differences between these results and the previously reported effects of these drugs, it is clear that AMPH and FEN influence feeding behavior in different ways.

Animals↗

Effects of cocaine, alone and in combination with task performance, on heart rate and blood pressure.

Eleven adult male subjects with histories of cocaine use participated in daily experimental sessions consisting of resting cardiovascular (heart rate, blood pressure) baseline measures followed by intranasal cocaine (4, 48 or 96 mg) administration and further cardiovascular monitoring. Subjects in Group I performed a learning task before and after cocaine administration, while subjects in Group II rested. Cocaine administration alone significantly increased heart rate up to 10 beats per minute (bpm) and mean arterial pressure (MAP) up to 15 mm/Hg. Task performance alone increased heart rate up to 8 bpm and MAP up to 10 mm/Hg. In combination, increases in heart rate up to 19 bpm and MAP up to 18 mm/Hg were observed. Thus, combinations of cocaine administration and task performance increased heart rate and blood pressure above levels observed following the occurrence of either activity alone. These results indicate the importance of understanding the effects of drugs within the environmental context in which they are taken.

Adult↗

Ethanol and cocaine interactions in humans: cardiovascular consequences.

Intranasal cocaine (COC) and oral ethanol (ETOH) were administered to nine research volunteers during daily experimental sessions. Following the determination of baseline cardiovascular indexes, an ETOH cocktail (0, 19.4, 38.7, or 58.1 g of ETOH in lemonade) was consumed over a ten-minute period. Cocaine hydrochloride (4, 48, 96 mg) was inhaled 25 minutes after the start of ETOH drinking. Breath samples were collected 50 minutes after the start of ETOH drinking to estimate blood alcohol level (BAL). The effect of these doses, alone and in combination, on heart rate (HR) and blood pressure (BP), while resting and while performing a serial acquisition task, were determined. COC and ETOH alone significantly increased HR up to 6 bpm without affecting BP. Combining the two highest doses of COC with the highest BAL increased HR by 20 bpm. During task performance, in the absence of drug, HR was increased up to 5 bpm, and BP was unchanged. Combining the highest COC dose and BAL with task performance increased HR by 40 bpm. Small increases in BP were also observed under these conditions. These results indicate that combinations of ETOH, COC and task performance produce greater increases in HR than BP, and, in addition, this increase in HR is greater than that observed following COC, ETOH, or task performance alone.

Adult↗