Ralph Spiga

Laboratory-Measured Aggressive Behavior of Women: Acute Tryptophan Depletion and Augmentation

Plasma L-tryptophan (Trp) reductions have been related to aggression increases in men. Impairment of serotonin synthesis and neurotransmission is one explanation. Using repeated-measures, this Trp manipulation study measured laboratory-induced aggression in 12 women after Trp augmentation (T+), depletion (T−), and food-restricted (fasting control) conditions. Participants were provoked with periodic subtraction of money from their task earnings by a (fictitious) partner. Aggression was defined as the number of point subtractions participants made from their fictitious partner. Participants completed five testing sessions under each condition. T+ decreased aggressive responses and T− increased aggressive responses. Post-hoc analyses showed changes in aggressive behavior were specific to women with higher fasting control plasma Trp, which is consistent with research demonstrating that men with higher levels of baseline Trp are more aggressive. These findings indicate that both T+ and T− can influence aggressive behavior and that certain subgroups of women may be more susceptible to serotonin manipulation.

Effects of nicotine on methadone self-administration in humans

The effects of nicotine abstinence, ad libitum smoking, and 0, 2, and 4 mg nicotine gum on methadone self-administration were investigated. Five methadone-maintained patients with a history of smoking (18-30 cigarettes/day) were recruited as subjects. Upon arrival expired carbon monoxide levels were measured to confirm self-reported abstinence of 10-12 h. At 30 min prior to the methadone self-administration session, two response options were concurrently available. When a 64-button press requirement (FR64) was completed, 10 ml of 0.054 mg/ml methadone solution, or vehicle, was delivered. Immediately following, and 30, 60, 90, and 120 min after the self-administration session, expired carbon monoxide levels and typical symptoms of nicotine withdrawal were assessed. Relative to abstinence, subjects consumed more methadone following the 4-mg nicotine gum and ad libitum smoking conditions. Ratings of cigarette craving were significantly less following ad libitum smoking or administration of 4-mg nicotine gum, than following abstinence. Implications for understanding opioid and nicotine interactions are discussed.

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 subjects 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.

Smoking cessation in women with cardiac risk: A comparative study of two theoretically based therapies

This gender-specific research study compares the relative effectiveness of two theory-based interventions targeting women who smoke. Women with coronary artery disease (CAD; n = 53) or CAD risk factors (n = 107) were randomly assigned to either coping-skills Relapse Prevention (RP) treatment or an educational/supportive treatment based on Health Belief Model (HBM) principles. RP was comparable, but not superior to HBM treatment, as indicated by the lack of differential smoking outcomes at 3 and 6 months. RP was more effective than HBM for women with low self-efficacy, as predicted. The presence of a smoking-related disease had a substantial effect on smoking status, in that the odds of being abstinent at 6 months were 2.2 times greater for non-diagnosed women when compared with CAD women. These findings indicate that more potent relapse prevention interventions are needed to increase cessation rates in women who smoke, especially those with established heart disease.

Compliance with tubercolosis treatment in methadone-maintained patients: Behavioral interventions

UNLABELLED Tuberculosis has increased dramatically in the United States. Noncompliance with treatment is high. The purpose of this investigation was to achieve compliance with prophylactic TB treatment and simultaneously decrease drug use in a high-risk group of intravenous drug users. Two studies were conducted. Study 1: Subjects were 9 chronic opiate users who tested positive for tuberculosis and were placed on isoniazid (INH) and methadone. Methadone was dispensed contingent upon INH ingestion throughout. A within-subject, A-B design with contingency management interventions on drug use was implemented. RESULTS Compliance with INH was 100% in 8 patients. Cocaine use remained high. Study 2: Two patients, meeting same criteria as Study 1, participated in a within-subject A-B multiple baseline design. Methadone was dispensed contingent upon INH ingestion throughout. Successive decreases in cocaine use were reinforced in the contingent phase. RESULTS Compliance with INH was high. During contingency, both patients had over 40% cocaine-free urine samples compared with 0% at baseline. This investigation serves as a model for achieving compliance with TB treatment in opiate users.

Human methadone self-administration: effects of diazepam pretreatment.

The effect of diazepam on methadone self-administration was examined. Five methadone-maintained patients with a history of benzodiazepine abuse were recruited. Patients were stabilized on 80 mg of methadone per day. After stabilization patients participated in methadone self-administration sessions. During each session, 128 presses (fixed ratio 128) of 1 button delivered 10 ml of 0.054 mg/ml methadone solution. The same number of button presses on a 2nd button delivered 10 ml of vehicle. Forty-five min prior to the self-administration session, 0 (placebo), 5, 10, or 20 mg per 70 kg body weight diazepam was administered. Ratings of drug liking, goodness, strength, and high were collected 5, 30, 60, 90, and 150 min after the end of the self-administration session. Diazepam pretreatment significantly decreased the amount of methadone consumed. The 10- and 20-mg diazepam doses significantly increased reports of good, like, strong, and high.

Assessment of the relative reinforcement value of smoking and drinking using a multiple-choice measurement strategy.

To examine the relative reinforcement value of smoking and drinking, separately and in combination, a multiple-choice questionnaire was administered to 78 individuals seeking outpatient treatment for concurrent tobacco and alcohol dependence. Participants made choices between pairs of substances and then between each substance and a series of monetary values. Results demonstrated that the combination (one cigarette and one drink) was preferred over each individual substance. The mean crossover monetary points for a cigarette (8.1 US dollars) and a drink (10.8 US dollars) were significantly lower than for the combination (13.75 US dollars). Correlational analyses revealed positive associations between drug reinforcement values and dependence-related measures. The utility of this measurement strategy in understanding and treating polydrug use is discussed.

Human Methadone Self-Administration and the Generalized Matching Law.

The present study examined whether in humans the generalized matching law described the relation between relative responding and relative drug intake by humans under concurrent variable interval variable interval (conc VI VI) schedules of drug reinforcement. Methadone-maintained patients, stabilized on 80 mg per day of methadone, were recruited and trained to button press for repeated deliveries of small volumes (10 ml) of 0.08 mg/ml methadone solution. In the training phase, deliveries of methadone or vehicle solution were arranged under conc VI VI schedules of reinforcement. The mean interval for the methadone and for the vehicle options was 60, 90, 120, 180, and 240 s. During another phase, responding on either of 2 buttons produced methadone solution. For the comparison option, the mean interval was 60, 90, 120, 180 or 240 s. For the concurrently available standard option, the mean interval was a constant 120 s. When methadone and vehicle were available, methadone was preferred to vehicle. When methadone was available at either option, the generalized matching law described the relation between relative response allocation and methadone intake. The results extend the generality of the matching law to human drug self-administration. The study also demonstrated the importance of reinforcement context as a determinant of human behavioral allocation.

Effects of nicotine on cooperative responding among abstinent male smokers.

The effects of nicotine on human cooperative responding in abstinent male smokers were examined. During episodes occurring at random times through a session, concurrently available cooperative and independent responses were maintained by points exchangeable for money. Cooperative responses simultaneously added points to counters marked “Your Earnings” and “Others Earnings” only if the subjects and another persons responses ostensibly coincided. Independent responses added points only to the counter marked “Your Earnings”. After the first daily session abstinent subjects smoked ad libitum, received either 0, 2 or 4 mg nicotine gum or abstained from smoking. Increases from this first session in time allocated to the cooperative response option, proportion of cooperative responses and cooperative response rate were significantly greater following ad libitum smoking or acute administration of 4 mg nicotine. No effects of nicotine abstinence were observed on independent response rate. These results suggest effects on sociability may maintain nicotine use and increase relapse risk in abstinent smokers.

Benzodiazepine-induced impairment of matching-to-sample performance in humans

The effects of benzodiazepines on a visual pattern matching-to-sample (MTS) task were examined in nine healthy male volunteers. The MTS task employed randomly generated checkerboard-like stimuli presented on a video display. The sample and two comparison stimuli were simultaneously presented. Nonmatching comparison stimuli were randomly generated to be 3.125, 6.25, 12.5, 25.0, 37.5, or 50.0 percent different from the sample. Subjects responded on left or right button manipulanda to identify the matching comparison stimulus. The nonmatching stimulus condition was maintained constant for a 60-sec component and the percentage difference of the nonmatching stimuli was systematically varied across multiple components. The effects of triazolam (2.25-9.0 micrograms/kg) and lorazepam (7.5-45 micrograms/kg) were examined in a within-subjects, double-blind, placebo-controlled study. Under placebo conditions, response rates and accuracy were a positive function of the nonmatching stimulus discriminability. Triazolam produced dose-related decreases in response rate at nonmatching stimulus conditions greater than or equal to 25%. Only the 9.0 micrograms/kg dose of triazolam decreased accuracy and this occurred across all nonmatching stimulus conditions. Lorazepam effects were qualitatively similar but less robust than those of triazolam.