Experimental & Clinical Psychopharmacology

Dose effects of triazolam and alcohol on cognitive performance in healthy volunteers.
Benzodiazepines and alcohol are widely used psychoactive substances that have performance-impairing effects. Research suggests that the impairment profiles for benzodiazepines and alcohol differ, although few cognitive psychopharmacological studies have directly compared these drugs. This double-blind, double-dummy, placebo-controlled, repeated measures study directly compared the acute dose effects of triazolam (0.125, 0.25 mg/70 kg) and alcohol (0.40, 0.80 g/kg) in 20 social drinkers. At doses that produced comparable psychomotor impairment, triazolam was more likely to impair several objective measures of cognitive performance (e.g., episodic memory, divided attention) and to slow performance across several measures. However, only alcohol impaired accuracy on the digit symbol substitution and semantic memory tasks. In addition to objective measures, both drugs impaired awareness of performance impairments (i.e., metacognition) such that participants overestimated impairment, and the magnitude of this effect was generally larger for alcohol. Only triazolam impaired other measures of metacognition (e.g., error detection on a choice reaction time task). Future research might examine the clinical implications of the performance impairments reported here given the widespread use of benzodiazepines and alcohol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Dose effects of triazolam and scopolamine on metamemory.
The present study compared the acute dose effects of the benzodiazepine triazolam and the anticholinergic scopolamine on metamemory (knowledge and awareness of one’s own memory) in a two-phase paradigm designed to assess effects on both monitoring and control components of metamemory in both semantic (general knowledge) and episodic memory (cued-recall) tasks. Placebo and 2 doses each of triazolam (0.125, 0.25 mg/70 kg, oral) and scopolamine (0.25, 0.50 mg/70 kg, subcutaneous) were administered to 80 healthy volunteers (16 per group) in a double-blind, double-dummy, independent groups design. Both triazolam and scopolamine impaired episodic memory (quantity and accuracy) but not semantic memory. Results suggested that both drugs impaired monitoring as reflected in absolute accuracy measures (impaired calibration in the direction of overconfidence) and control sensitivity (the relationship between confidence and behavior). Overall, the results did not provide evidence for differences between triazolam and scopolamine in memory or metamemory. In addition to the clinical relevance of the observed effects, this study adds to the accumulating body of cognitive psychopharmacological research illustrating the usefulness of drug-induced amnesia as a vehicle to explore memory and metamemory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
The relationship between in-treatment abstinence and post-treatment abstinence in a smoking cessation treatment.
Previous research has indicated that abstinence early in a smoking cessation program is predictive of successful posttreatment abstinence. However, it has not been established whether or not this effect is independent of other in-treatment abstinence patterns. In this paper the relationship between three potentially important aspects of in-treatment smoking abstinence and posttreatment smoking abstinence are examined: early abstinence, extended abstinence, and end-of-treatment abstinence. We examined the relationship between smoking behavior measured each weekday over 70 visits (approximately 14 weeks) of a contingency management smoking cessation program and at a follow-up visit 6 months after study entry (3 months after the scheduled end of treatment). Ninety-five of 102 participants were successfully followed-up. Seven of these 95 participants were confirmed abstinent. Early abstinence, defined as abstinence during the first 10 treatment visits, was significantly and independently related to follow-up abstinence (OR = 56.67 [7.29–440.63]). Extended abstinence and end-of-treatment abstinence were related to follow-up abstinence, but not independent of early abstinence based on multiple regression models. Inclusion of a variety of demographic and environmental characteristics did not significantly alter this relationship. Thus, consistent with the previous literature, the establishment of early abstinence appears to be crucial to establishing longer-term abstinence, independent of other in-treatment abstinence patterns. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
A contingency-management intervention to promote initial smoking cessation among opioid-maintained patients.
Prevalence of cigarette smoking among opioid-maintained patients is more than threefold that of the general population and associated with increased morbidity and mortality. Relatively few studies have evaluated smoking interventions in this population. The purpose of the present study was to examine the efficacy of contingency management for promoting initial smoking abstinence. Forty methadone- or buprenorphine-maintained cigarette smokers were randomly assigned to a contingent (n = 20) or noncontingent (n = 20) experimental group and visited the clinic for 14 consecutive days. Contingent participants received vouchers based on breath carbon monoxide levels during Study Days 1 to 5 and urinary cotinine levels during Days 6 to 14. Voucher earnings began at $9.00 and increased by $1.50 with each subsequent negative sample for maximum possible of $362.50. Noncontingent participants earned vouchers independent of smoking status. Although not a primary focus, participants who were interested and medically eligible could also receive bupropion (Zyban). Contingent participants achieved significantly more initial smoking abstinence, as evidenced by a greater percentage of smoking-negative samples (55% vs. 17%) and longer duration of continuous abstinence (7.7 vs. 2.4 days) during the 2 week quit attempt than noncontingent participants, respectively. Bupropion did not significantly influence abstinence outcomes. Results from this randomized clinical trial support the efficacy of contingency management interventions in promoting initial smoking abstinence in this challenging population. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Nicotine primes attention to competing affective stimuli in the context of salient alternatives.
Despite the importance of the subject, the effects of nicotine on the interplay between affect and attentional bias are not clear. This interplay was assessed with a novel design of the Primed Attentional Competition Task (PACT). It included a 200-ms duration emotional priming picture (negative, positive, or neutral) followed by a dual-target picture of two emotional faces side-by-side. A second task included an emotional priming picture followed by a single emotional target picture in a classic affective priming (CAP) task, assessing reaction time to identify the valence. Smokers completed the tasks in a double-blind repeated measures design wearing a nicotine patch on one day and a placebo patch on the other day. Consistent with hypotheses, nicotine enhanced the effectiveness of positive primes to bias first gaze-fixations (FGFs) toward neutral pictures relative to negative pictures and attenuated the effectiveness of negative primes on FGFs toward negative pictures, but did not bias performance in the CAP task where competing target stimuli were not present. These effects of nicotine on affective priming and attentional bias toward competing reinforcers may contribute to smoking motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Testing the influence of external and internal cues on smoking motivation using a community sample.
Exposing smokers to either external cues (e.g., pictures of cigarettes) or internal cues (e.g., negative affect induction) can induce urge to smoke and other behavioral and physiological responses. However, little is known about whether the two types of cues interact when presented in close proximity, as is likely the case in the real word. Additionally, potential moderators of cue reactivity have rarely been examined. Finally, few cue-reactivity studies have used representative samples of smokers. In a randomized 2 × 2 crossed factorial between-subjects design, the current study tested the effects of a negative affect cue intended to produce anxiety (speech preparation task) and an external smoking cue on urge and behavioral reactivity in a community sample of adult smokers (N = 175), and whether trait impulsivity moderated the effects. Both types of cues produced main effects on urges to smoke, despite the speech task failing to increase anxiety significantly. The speech task increased smoking urge related to anticipation of negative affect relief, whereas the external smoking cues increased urges related to anticipation of pleasure; however, the cues did not interact. Impulsivity measures predicted urge and other smoking-related variables, but did not moderate cue-reactivity. Results suggest independent rather than synergistic effects of these contributors to smoking motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral effects of acute and chronic antidepressant treatments.
Adult hippocampal neurogenesis has been implicated in the pathophysiology of depression and in the therapeutic effects of antidepressant drugs. Current immunohistochemical methods that study neurogenesis are time consuming and labor intensive. Therefore, a significantly more rapid flow cytometric method was characterized to measure neurogenesis in the adult mouse brain. The sensitivity of mice to the effects of antidepressant treatments is dependent on genetic background. Thus, studies were conducted comparing the responsiveness of 2 inbred mouse strains, MRL/MpJ and C57BL/6J, to the acute and chronic effects of antidepressants on neurochemistry and behavior. Acutely, MRL/MpJ mice displayed more robust behavioral and neurochemical responses to pharmacologically distinct antidepressants than C57BL/6J mice. Chronic administration of the antidepressant drugs fluoxetine and desipramine produced robust elevations in hippocampal cell proliferation and brain-derived neurotrophic factor (BDNF) protein levels in MRL/MpJ mice. C57BL/6J mice treated similarly with antidepressant drugs were mainly unresponsive on these measures. Mice were tested in the novelty-induced hypophagia (NIH) paradigm to examine a behavioral response associated with chronic, but not acute, antidepressant treatment. Only MRL/MpJ mice were behaviorally responsive to chronic antidepressant administration in the NIH paradigm. The positive effects of chronic antidepressants on hippocampal cell proliferation and BDNF paralleled the ability of these drugs to produce changes in NIH behavior. These studies highlight the advantages of using flow cytometry to study hippocampal neurogenesis and identify the MRL/MpJ mouse as a strain with superior response to antidepressant drug treatments that may lead to a better understanding of the genetics behind antidepressant efficacy and sensitivity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Effects of acute progesterone administration upon responses to acute psychosocial stress in men.
Animal studies suggest that neuroactive steroids, in particular progesterone and its metabolites, have stress-dampening effects. However, few studies have explored these effects in humans. In this study, we investigated the effects of acute progesterone administration on responses to the Trier Social Stress Test (TSST). Healthy men participated in the TSST 3.5 hrs after intramuscular injection of 0, 50, or 100 mg progesterone (N = 16, 14, and 14). We measured cardiovascular (heart rate, blood pressure), hormonal (plasma adrenocorticotrophic hormone, cortisol, and noradrenaline), and subjective (e.g., anxiety, arousal) responses to stress in the three groups. Before the TSST, progesterone injections increased plasma levels without altering physiological or subjective states. Stress produced its expected physiological and subjective effects among placebo-treated individuals. Progesterone 50 mg attenuated peak increases in plasma cortisol and reduced changes in negative mood and alertness after stress, yet it increased plasma noradrenaline and systolic blood pressure. Progesterone 100 mg also attenuated stress-induced increases in alertness and arousal, yet it potentiated stress-induced increases in diastolic pressure. Thus, progesterone dampened some of the psychological effects of stress but produced inconsistent effects on physiological stress responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Computer-assisted cognitive rehabilitation for the treatment of patients with substance use disorders: A randomized clinical trial.
The purpose of this study was to examine the comparative efficacy of cognitive rehabilitation as an intervention for substance misuse. Patients with substance use disorders entering long-term residential care (N = 160) were randomly assigned to one of two conditions: (a) standard treatment plus computer-assisted cognitive rehabilitation (CACR), which was designed to improve cognitive performance in areas such as problem solving, attention, memory, and information processing speed; and (b) an equally intensive attention control condition consisting of standard treatment plus a computer-assisted typing tutorial (CATT). Participants were assessed at baseline, during treatment, at treatment completion, and 3-, 6-, 9-, and 12-month follow-up. Intent-to-treat analyses showed that, compared with those randomized to CATT, patients who received CACR were significantly more engaged in treatment (e.g., higher ratings of positive participation by treatment staff, higher ratings of therapeutic alliance), more committed to treatment (e.g., longer stays in residence) and reported better long-term outcomes (e.g., higher percentage of days abstinent after treatment). Mediational analyses revealed the positive comparative effect of CACR on abstinence during the year after treatment was mediated by treatment engagement and length of stay in residence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)
Delay discounting in current and former marijuana-dependent individuals.
Studies have found that a variety of drug-dependent groups discount delayed rewards more than matched controls. This study compared delay discounting for a hypothetical $1,000 reward among dependent marijuana users, former dependent marijuana users, and matched controls. Discounting of marijuana was also assessed in the currently marijuana-dependent group. No significant differences in discounting were detected among the groups; however, currently dependent users showed a trend to discount money more than the other 2 groups. Within the dependent marijuana group, marijuana was discounted more than money, and discounting for money and marijuana was significantly and positively correlated. Regression analyses indicated that delay discounting was more closely associated with tobacco use than marijuana use. A variety of questionnaires were also administered, including impulsivity questionnaires. Dependent marijuana users scored as significantly more impulsive on the Impulsiveness subscale of the Eysenck Impulsiveness–Venturesomeness–Empathy questionnaire than controls. However, the 3 groups did not significantly differ on several other personality questionnaires, including the Barratt Impulsivity Scale—11. The Stanford Time Perception Inventory Present–Fatalistic subscale was positively correlated with money and marijuana discounting, indicating that a greater sense of powerlessness over the future is related to greater delay discounting. Results suggest that current marijuana dependence may be associated with a trend toward increased delay discounting, but this effect size appears to be smaller for marijuana than for previously examined drugs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)

Experimental and Clinical Psychopharmacology - Vol 18, Iss 1