Effects of delays on human performance on a temporal discrimination procedure: evidence of a choose-short effect.

Studies of temporal discrimination in non-human subjects have reliably shown a choose-short effect: higher matching accuracy on short-duration-sample trials than on long-duration-sample trials. This effect occurs as a function of increasing the delay between the onset of sample and comparison stimuli in a delayed matching-to-sample procedure. The present experiment investigated whether the choose-short effect could be demonstrated in human subjects under conditions which paralleled those used with non-human subjects. Subjects responded under a discrete-trial procedure in which they were required to push one of two buttons depending on the duration of a sample stimulus (a blue square on a computer monitor). Delays (0, 8, 16, and 32s) separated sample and comparison stimuli (two white boxes) and were tested both within and across several sessions. Intermediate durations (probe stimuli between 2 and 4s) were also presented. The addition of a delay between the sample and comparison stimuli produced a bias to judge intervals as short when the 8 and 32-s delays were tested across sessions and when the 0, 16, and 32-s delays were tested within the same session. Thus, the choose-short effect was produced in human subjects using the interval bisection procedure regardless of delay length.

Laboratory and psychometric measurements of impulsivity among violent and nonviolent female parolees.

BACKGROUND: Female parolees participated in a study to determine the relationship between behavioral and psychometric measures of impulsivity and their previous criminal history. METHODS: Subjects were assigned to a violent (n = 10) or nonviolent group (n = 20) based upon their criminal history. Subjects were given two response options defined as: 1) an impulsive choice--small monetary reward (5 cents) after a short fixed delay of 5 sec, and 2) a self-control choice--a larger monetary reward (15 cents) after a variable longer delay initially set at 15 sec. The measure of impulsivity in this behavioral choice procedure was the number of trials on which the subject selected the impulsive option. This definition of impulsivity is based upon an extensive experimental literature in nonhumans and humans related to delay of gratification, that is, the ability to tolerate long delays imposed between the initiation of behavior and the presentation of a reinforcer. RESULTS: Our results indicated that the violent female subjects selected the impulsive option significantly more often than the nonviolent female parolees. CONCLUSIONS: The correlation between impulsive and aggressive responses among the female parolees was nonsignificant and negative, in contrast to a significant positive correlation previously reported among male parolees.

Studies of violent and nonviolent male parolees: I. Laboratory and psychometric measurements of aggression.

Male parolees were recruited into a laboratory study to determine the relationship between their previous aggression history, psychometric measures of aggression, and behavioral measures of aggressive responding using a laboratory methodology: the Point Subtraction Aggression Paradigm. Subjects were assigned to a violent or nonviolent group based upon their criminal history. Subjects participated in sessions in which they were given three response options defined as: (1) nonaggressive responding which earned money, (2) aggressive responding which ostensibly subtracted money from another fictitious person, (This responding was defined as aggressive since it resulted in the ostensible delivery of an aversive stimulus (subtraction of money) to another person), and (3) escape which protected the subject's earnings from subtractions initiated by the other person. Results indicated that the violent subjects emitted significantly more aggressive responses than subjects in the nonviolent group. The number of aggressive responses parolees emitted was significantly correlated with most psychometric measures of aggression. This study provides external validity for our laboratory measurement of human aggressive responding, since aggressive responding was directly related to violent criminal histories.

Studies of violent and nonviolent male parolees: II. Laboratory and psychometric measurements of impulsivity.

Males parolees were recruited into a laboratory study to determine the relationship between their previous criminal history (violent versus nonviolent), and behavioral and psychometric measures of impulsivity. During sessions, subjects were given two response options defined as: 1) an impulsive choice--small monetary reward after a short fixed delay; and 2) a self-control choice--a larger monetary reward after a variable longer delay. Based upon an extensive experimental literature in animals and humans related to delay of gratification, the degree of impulsivity was defined as the proportion of trials on which the subject selected the impulsive option. Our results indicated that the violent subjects selected the impulsive option significantly more often than the nonviolent parolees. The number of impulsive responses parolees emitted was significantly correlated with the number of aggressive responses reported in an earlier paper. This study provides support for the relationship between impulsivity and aggression among male parolees.

Effects of ammonium chloride on urinary pH and cigarette smoking behavior.

We determined the effects of acidification of urinary pH on cigarette smoking behavior to assess the postulated relationships between stress, urinary pH, and cigarette smoking. Urine was acidified by short-term administration of 12.5, 25, and 50 mg/kg ammonium chloride and long-term administration of 50 mg/kg ammonium chloride. Measurements of cigarette smoking behavior included the number of cigarettes smoked as well as automated measures of puff frequency and duration. Short- and long-term administration of ammonium chloride induced decreases in urinary pH but failed to induce any substantial changes in number of cigarettes smoked, puff frequency, or puff duration.

Effects of increasing urinary pH on cigarette smoking.

We evaluated the effects of increasing urinary pH on sensitive automated measures of cigarette smoking behavior. Urine was alkalized by oral doses of 50 or 75 mg/kg sodium bicarbonate. Measurements of cigarette smoking behavior included the number of cigarettes smoked and automated measures of puff frequency and duration. The sodium bicarbonate resulted in little or no change in the number of cigarettes smoked, but in five of the seven subjects frequency and duration of cigarette puffs after sodium bicarbonate decreased 10% to 15%. The small decreases in cigarette smoking brought about by sodium bicarbonate cannot be expected to have significant overall effects.

Effects of cigarettes on saliva cortisol levels.

We determined the effects of cigarette deprivation and smoking on saliva cortisol levels in the presence and absence of an operant, monetarily reinforced work task. Subjects were randomly exposed to the following four experimental conditions over successive sessions: no smoking, smoking, no smoking + work, and smoking + work. Measurements of cortisol levels in saliva were determined before and after each daily session. Saliva cortisol levels declined from the beginning to the end of sessions and the end-of-session saliva cortisol levels were not affected by any of the four experimental conditions. Increased cigarette smoking in the presence of the work task also did not affect saliva cortisol levels. Our data do not support: reports of increased cortisol levels as a consequence of smoking or theories relating cortisol and endorphin release to nicotine habituation.

Drug excretion in human breast milk: principles, pharmacokinetics and projected consequences.

The excretion of drugs in human breast milk is reviewed with regard to milk production, composition, feeding patterns and mechanisms of drug transfer into milk. Fundamental principles of breast milk excretion are used to construct a pharmacokinetic approach useful for the study of most drugs. An infant-modulated 3-compartment open model is proposed for drug distribution and elimination in the breast feeding woman. Milk/plasma drug concentration ratios are projected on the basis of pH partitioning. While some studies confirm these projections, other studies demonstrate a need to consider additional factors such as lipid solubility and protein binding characteristics of a drug in milk. Data are lacking for most drugs and hence dosing via milk or risk to the infant remains speculative. Very few pharmacokinetic studies of both milk and infant plasma were found. A review of selected drug classes cites available information as a basis for future studies. Few drugs are contraindicated in breast feeding women, but supportive data for either proscriptions or permissive statements are often lacking. A neglected but potentially serious infant risk--impaired behaviour and development--is discussed from the standpoint of emerging animal data. Conceptually valid and comprehensive studies on drug excretion in breast milk are needed if this valuable nutrient for infants is to be made available safely.

Effects of smoking different doses of nicotine on human aggressive behavior.

A new methodology was employed to study the effects of drugs on human aggressive behavior in a laboratory situation. The effects of not smoking, smoking a low nicotine dose (0.42 mg/cigarette), and smoking a high nicotine dose (2.19 mg/cigarette) on human nonaggressive and aggressive responding was determined. A nonaggressive response, which resulted in the accumulation of money, was continuously available to the subject. Two different aggressive responses were also available: the ostensible subtraction of money from, and the ostensible presentation of a 1-s blast of white noise to a (fictitious) person. Aggressive responding was elicited by subtracting money from the research subjects, which was attributed to a fictitious person paired with the research subject randomly each day. Nicotine, administered with experimental cigarettes, produced dose-dependent decrease in both types of aggressive responding elicited by low or high frequency subtractions of money attributed to another person. Generally, the more aggressive response option, i.e., subtraction of money from another person, decreased more following nicotine administration. Smoking the same doses of nicotine increased nonaggressive monetary reinforced responding. This indicates that the suppressant effects of nicotine on aggressive responding was not due to a non-specific depressant action.

Acute effects of D-fenfluramine on simultaneous measures of aggressive escape and impulsive responses of adult males with and without a history of conduct disorder.

RATIONALE: The role of serotonin in human aggression was evaluated by administering D-fenfluramine and comparing the effects on laboratory measures of aggression, escape and impulsivity among subjects with and without a history of conduct disorder. METHODS: Ten male subjects with a history of criminal behavior participated in experimental sessions that measured aggressive and impulsive responses. Five subjects had a history of childhood conduct disorder (CD+) and five control subjects did not. Aggression was measured using the Point Subtraction Aggression Paradigm (PSAP), which provides subjects with an aggressive, escape and monetary reinforced response options. Impulsive responses were measured using a paradigm that gives subjects choices between small rewards after short delays versus larger rewards after long delays. RESULTS: Acute doses (0.1, 0.2 and 0.4 mg/kg) of D-fenfluramine produced significant decreases in aggressive responses in CD+ subjects and large decreases in escape responses for CD+ subjects and smaller decreases for control subjects. Impulsive responses were decreased slightly and monetary reinforced responses were not changed in either group. Decreases in aggressive responses were not selective, since escape responses were also decreased, but such effects could not be attributed to a non-specific sedative action because monetary reinforced responses were increased and reaction times were decreased, indicative of central nervous system stimulation. CONCLUSIONS: Release of serotonin by D-fenfluramine is the possible mechanism for reductions in aggressive responses. These results are consistent with a large body of data linking reduced serotonin function and aggressive behavior.

Fenfluramine effects on impulsivity in a sample of adults with and without history of conduct disorder.

RATIONALE: The role of serotonin in impulsivity was examined by administering the serotonin-releasing drug, d,l-fenfluramine, and measuring effects on impulsive responding of male subjects with and without a history of conduct disorder (CD) under controlled laboratory conditions. METHODS: Five adult male subjects with a history of CD and five matched controls were recruited into a study to determine the acute effects of d,l-fenfluramine on a laboratory measure of impulsive behavior. This laboratory measure, based upon delay of gratification, presented subjects with choices between a small reward after a short delay and a larger reward after a longer delay. Impulsive behavior was indicated by frequent choices for the smaller reward. RESULTS: Acute oral doses of d,l-fenfluramine (0.21, 0.42, and 0.85 mg/kg) produced decreases in the number of impulsive choices in all subjects with a history of CD, but had no effect on the control subjects. CONCLUSIONS: This data suggests that a deficit in serotonin and/or dopamine may play a role in impulsivity in CD subjects, and drugs which act to reduce this biological deficit can reduce impulsiveness.

Effects of d,l-fenfluramine on aggressive and impulsive responding in adult males with a history of conduct disorder.

RATIONALE: The role of serotonin in aggression and impulsivity was examined by administering the serotonin-releasing drug, d, l-fenfluramine and measuring effects on aggressive and impulsive responding under controlled laboratory conditions. METHODS: Ten male subjects with a history of conduct disorder and criminal behavior participated in experimental sessions, which measured aggressive and impulsive responses. Aggression was measured using the Point subtraction Aggression paradigm (PSAP), which provides subjects with an aggressive, escape and monetary reinforced response options. Impulsive responses were measured using a paradigm which provided subjects with choices between small rewards after short delays versus larger rewards have long delays. RESULTS: Acute challenge doses (0.2,0.4 and 0.8 mg/kg) of d,l-fenfluramine produced significant dose-dependent decreases in aggressive and impulsive responses. Escape and monetary reinforced responses were not significantly changed. Decreases in aggressive responses were therefore selective, because escape responses were not affected, and could not be attributed to a non-specific sedative action because monetary reinforced responses were slightly increased. CONCLUSIONS: Release of serotonin and/or reuptake blockade by d,l-fenfluramine is the possible mechanism for reductions in aggression and impulsivity. These results are consistent with a large body of data linking reduced serotonin function and aggressive behavior and impulsivity.

Human aggressive responding during acute tobacco abstinence: effects of nicotine and placebo gum.

Aggressive and point maintained operant responding of heavy nicotine dependent male tobacco smokers were measured during five 25-min sessions conducted over an 8-h period. Responding under three tobacco abstinence conditions was compared to responding during a baseline condition of ad libitum smoking of the subject's preferred brand of cigarettes. The three tobacco abstinence conditions were: (1) placebo gum, (2) nicotine gum or (3) no gum. Under placebo and nicotine gum conditions, subjects were given two pieces of placebo or 2 mg nicotine gum to chew for 30 min prior to each session. Expired air carbon monoxide (CO) levels were measured at the end of each session to monitor smoking under baseline conditions and compliance with nonsmoking requirements under abstinence conditions. Aggressive responding was increased in no gum and placebo gum conditions, with the highest frequency of aggressive responding occurring under no-gum conditions. Aggressive responding during nicotine gum conditions did not differ from baseline ad libitum tobacco smoking. Point maintained responding was either not affected or decreased under placebo and no-gum conditions. These results provided objective data consistent with clinical reports of increased irritability among dependent tobacco smokers during acute tobacco abstinence.

Acute effects of marijuana smoking on aggressive, escape and point-maintained responding of male drug users.

Aggressive, escape and point-maintained operant responding of male marijuana smokers were measured during six 25-min sessions conducted over an 8-h experimental day. Aggressive responding ostensibly subtracted points exchangeable for money from another subject. Escape responding protected the subject's counter from point subtractions initiated by the other subject for some period of time. Aggressive and escape responding were engendered by subtracting points from the subjects and maintained by initiation of intervals free of point subtractions. Point subtractions presented to the subjects were attributed to other persons. Subjects earned points exchangeable for money on a third response option. Subjects participated in one session prior to smoking and five sessions after smoking. Subjects smoked placebo or three different potencies of active marijuana cigarettes. Marijuana smoking effects on escape responding were not significant and depended upon the frequency of provocation. Point-maintained responding was decreased after marijuana smoking. Aggressive responding was increased for the first hour after smoking and returned to placebo levels later in the day. These effects of marijuana smoking on aggressive responding are discussed in terms of subject characteristics, particularly drug use history.

Effects of acute administration of diazepam and d-amphetamine on aggressive and escape responding of normal male subjects.

Normal males participated in sessions providing two operant response options and were administered either diazepam (study I and II) or d-amphetamine (study II). The acute effects of diazepam on human aggressive responding, which ostensibly subtracted points from another person, were determined in study I. Study II was conducted to determine the extent to which social context and response consequence influenced diazepam (study I) and d-amphetamine (previous research) effects on aggressive responding. In study II, the other response option was escape responding which protected the subject's counter from point losses. Aggressive and escape responding were engendered by subtracting points from the subject's counter, and maintained by initiation of intervals free of point loss. Point subtractions were attributed to the other person (study I) or to a machine (study II). Responding to accumulate points exchangeable for money was available in both studies. Acute diazepam administration decreased aggressive responding in most subjects (study I), slightly increased escape responding (study II), and decreased responding to accumulate points. In study II, d-amphetamine increased both escape responding and responding to accumulate points. The effects of d-amphetamine and diazepam were altered by the instructed source of point loss.

Effects of d-amphetamine on human aggressive behavior.

Male research subjects were administered placebo and three doses of d-amphetamine (5, 10 and 20 mg/70 kg) in a laboratory situation which provided both aggressive and non-aggressive response options. The non-aggressive response was button pressing maintained by presentation of points exchangeable for money at the end of the session. The aggressive response was button pressing on a separate manipulanda which ostensibly subtracted points from a fictitious partner. Aggressive responding was elicited by subtracting points from the research subjects which was attributed to the fictitious partner. d-Amphetamine increased both aggressive and non-aggressive responding, particularly at 5 and 10 mg/70 kg. At the highest dose (20 mg/70 kg), aggressive responding decreased to levels similar to those observed during placebo sessions, while monetary reinforced responding remained elevated.

Prolactin response to buspirone was reduced in violent compared to nonviolent parolees.

A neuroendocrine challenge procedure was carried out in male and female parolees. The parolees were divided into violent and non-violent groups based upon their criminal history. Buspirone (0.4 mg/kg), a 5-HT1a agonist, was used as the challenge agent and plasma prolactin levels were determined. The violent parolees had a blunted prolactin response compared to the non-violent parolees. While reduced serotonergic activity may account for this difference, the pharmacology of buspirone and control of prolactin release suggest a role for dopamine. A reduced serotonergic response would be consistent with a large body of data linking reduced serotonin function and aggressive behavior. While the mechanism is not definite, these data clearly provide evidence for an altered and blunted biological response in parolees with a history of violence.

The effects of tryptophan depletion and loading on laboratory aggression in men: time course and a food-restricted control.

Some studies have shown that sharp reduction of L-tryptophan (Trp) concentration in plasma results in increases in laboratory-measured aggression. Conversely, raising plasma Trp has blunted aggression. These effects are presumably due to impaired or enhanced serotonin synthesis and neurotransmission in the brain. In this study, the laboratory-measured aggressive behavior of eight men under both Trp depletion (T-) and Trp loading (T+) conditions was compared to their aggressive behavior under food-restricted control conditions (overnight fast without an amino acid beverage). Subjects were provoked by periodic subtraction of money which was attributed to a fictitious other participant, and aggression was defined as the number of retaliatory responses the subject made ostensibly to reduce the earnings of the (fictitious) other participant. Following ingestion of the T- beverage, aggressive responding was significantly elevated relative to the food-restricted control condition, and this increased aggressive behavior became more pronounced across behavioral testing sessions on a time-course which paralleled previously documented decreases in plasma Trp concentrations. In contrast, no changes were observed in aggressive responding under T+ conditions relative to food-restricted conditions. These within-subject behavioral changes under depleted plasma Trp conditions support earlier indications of a role of serotonin in regulating aggression.

Reinforcer interactions under concurrent schedules of food, water, and intravenous morphine.

Responding by six rats was maintained under a concurrent chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9 ) of food, water, and morphine presentations. The subjects had continuous access to the schedule contingencies on a reversed 12-h light-dark cycle. Local rates and temporal patterns were very similar for responding maintained by the three reinforcers with food and water intake occurring predominantly during the dark cycle, while morphine infusions were evenly distributed. Food and water extinction (24-h duration) decreased the number of ratios completed on both the food and water levers. Moreover, food extinction resulted in a large increase in I.V. morphine self-administration. Morphine extinction increased responding on the morphine lever while almost eliminating responding on the water lever. Changes in the dose of morphine (2.5-40 mg/kg/injection) did not significantly affect food and water intake, but were inversely related to responding on the morphine lever. Saline substitutions resulted in effects similar to those observed during morphine extinction. The schedule used in this study provides a method for examining the specificity of a number of pharmacological and neurochemical manipulations.

Tryptophan depletion and aggressive responding in healthy males.

In order to study the effect of decreasing plasma tryptophan levels on aggressive responding in a controlled laboratory setting, we administered two doses (25 g and 100 g) of a tryptophan-free amino acid mixture to ten healthy male subjects after 24 h of a low tryptophan diet. Subjects were screened for current or past psychiatric, or non-psychiatric medical illness. Aggressive responding on a free-operant laboratory measure of aggression (the Point Subtraction Aggression Paradigm) and plasma tryptophan levels were measured before and after drinking the amino acid mixture. There was a significant increase in aggressive responding 5 h after the 100 g mixture and a significant increase in aggressive responding 6 h after the 25 g mixture compared to a baseline day when no drink was administered. There was also a significant decrease in plasma tryptophan at 5 hours after ingestion compared to baseline for both doses of amino acid mixture. This study supports the hypothesis that tryptophan depletion increases aggressive responding in healthy males in a laboratory setting, probably by decreasing brain serotonin.