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Experimental and Clinical Psychopharmacology - Vol 23, Iss 1

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Experimental & Clinical Psychopharmacology Experimental and Clinical Psychopharmacology seeks to promote the discipline of psychopharmacology in its fullest diversity. Psychopharmacology necessarily involves behavioral change, psychological processes, or their physiological substrates as one central variable and psychopharmacological agents as a second central variable. Such agents will include drugs, medications, and chemicals encountered in the workplace or environment.
Copyright 2015 American Psychological Association
  • A brief history of the development of antidepressant drugs: From monoamines to glutamate.
    Major depressive disorder (MDD) is a chronic, recurring, and debilitating mental illness that is the most common mood disorder in the United States. It has been almost 50 years since the monoamine hypothesis of depression was articulated, and just over 50 years since the first pharmacological treatment for MDD was discovered. Several monoamine-based pharmacological drug classes have been developed and approved for the treatment of MDD; however, remission rates are low (often less than 60%) and there is a delayed onset before remission of depressive symptoms is achieved. As a result of a “proof-of-concept” study in 2000 with the noncompetitive NMDA antagonist ketamine, a number of studies have examined the glutamatergic systems as viable targets for the treatment of MDD. This review will provide a brief history on the development of clinically available antidepressant drugs, and then review the possible role of glutamatergic systems in the pathophysiology of MDD. Specifically, the glutamatergic review will focus on the N-methyl-D-aspartate (NMDA) receptor and the efficacy of drugs that target the NMDA receptor for the treatment of MDD. The noncompetitive NMDA receptor antagonist ketamine, which has consistently produced rapid and sustained antidepressant effects in MDD patients in a number of clinical studies, has shown the most promise as a novel glutamatergic-based treatment for MDD. However, compounds that target other glutamatergic mechanisms, such as GLYX-13 (a glycine-site partial agonist at NMDA receptors) appear promising in early clinical trials. Thus, the clinical findings to date are encouraging and support the continued search for and the development of novel compounds that target glutamatergic mechanisms. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Allopregnanolone association with psychophysiological and cognitive functions during acute smoking abstinence in premenopausal women.
    Nicotine response may predict susceptibility to smoking relapse. Allopregnanolone, a neuroactive steroid metabolized from progesterone, has been shown to be associated with several symptoms of nicotine response. We sought to explore the association between allopregnanolone and response to nicotine during acute smoking abstinence in premenopausal women. Participants completed 2 nicotine-response laboratory sessions, 1 in their follicular (low allopregnanolone) and 1 in their luteal (high allopregnanolone) menstrual phase, on the fourth day of biochemically confirmed smoking abstinence. During the laboratory sessions, participants self-administered a nicotine nasal spray and completed a timed series of cardiovascular, cognitive, and subjective assessments of response to nicotine. The relationships of allopregnanolone with baseline values and change scores of outcome measures were assessed using covariance pattern modeling. Study participants (N = 77) had a mean age of 29.9 (SD = 6.8) years and smoked an average of 12.2 (SD = 4.9) cigarettes per day. Allopregnanolone concentration measured before nicotine administration was positively associated with systolic (β = 0.85, p = .04) and diastolic blood pressure (β = 1.19, p <.001) and self-report of physical symptoms (β = 0.58, p <.001), dizziness (β = 0.88, p <.01), jitteriness (β = 0.90, p = .04), and pleasantness (β = 2.05, p = .04). Allopregnanolone also had significant positive associations with change in cognition following nicotine nasal spray administration, specifically discriminability as a measure of attention (β = 1.15, p = .05) and response bias as a measure of impulsivity (β = 0.13, p = .02). These data suggest that allopregnanolone may be related to cardiovascular and subjective physical state during acute smoking abstinence, as well as cognitive response to nicotine. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Acute effects of nicotine on alcohol cue-reactivity in nondependent and dependent smokers.
    Evidence from alcohol self-administration studies suggests that nicotine replacement therapy may influence subjective and behavioral responses to alcohol. However, its effect on alcohol cue-reactivity is unknown. The present study examined the impact of acutely administered nicotine on subjective responses to alcohol-focused pictorial stimuli. In a mixed within/between-subjects design, nondependent smokers (n = 51) and dependent smokers (n = 45) who socially drink were assigned to either a nicotine (4 mg) or placebo lozenge condition following overnight tobacco abstinence. Following lozenge absorption, participants viewed neutral images followed by alcohol-focused pictures. Craving measures for alcohol and tobacco were completed at baseline, following lozenge absorption, following neutral cues, and following alcohol cues. The presentation of alcohol cues increased alcohol-related craving relative to neutral cues, especially among men, but the administration of nicotine did not influence the magnitude of these effects. Nicotine lozenges were found to decrease intentions to smoke and withdrawal-related craving in dependent but not in nondependent smokers. Finally, the presentation of alcohol cues was found to increase intentions to smoke relative to neutral cues across participants regardless of lozenge condition. Findings suggest that although the presentation of alcohol cues can increase alcohol- and tobacco-related cravings in smokers, such effects do not appear to be affected by acute nicotine administration. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • The motivational salience of cigarette-related stimuli among former, never, and current smokers.
    While smokers are known to find smoking-related stimuli motivationally salient, the extent to which former smokers do so is largely unknown. In this study, we collected event-related potential (ERP) data from former and never smokers and compared them to a sample of current smokers interested in quitting who completed the same ERP paradigm prior to smoking cessation treatment. All participants (n = 180) attended 1 laboratory session where we recorded dense-array ERPs in response to cigarette-related, pleasant, unpleasant, and neutral pictures and where we collected valence and arousal ratings of the pictures. We identified 3 spatial and temporal regions of interest, corresponding to the P1 (120–132 ms), early posterior negativity (EPN; 244–316 ms), and late positive potential (LPP; 384–800 ms) ERP components. We found that all participants produced larger P1 responses to cigarette-related pictures compared to the other picture categories. With the EPN component, we found that, similar to pleasant and unpleasant pictures, cigarette-related pictures attracted early attentional resources, regardless of smoking status. Both former and never smokers produced reduced LPP responses to cigarette-related and pleasant pictures compared to current smokers. Current smokers rated the cigarette-related pictures as being more pleasant and arousing than the former and never smokers. The LPP and picture-rating results suggest that former smokers, like never smokers, do not find cigarette-related stimuli to be as motivationally salient as current smokers. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Sexual discounting among high-risk youth ages 18–24: Implications for sexual and substance use risk behaviors.
    Youth under 25 show substantial sexual and substance use risk behaviors. One factor associated with risk behaviors is delay discounting, the devaluation of delayed outcomes. This study determined if delay discounting for sexual outcomes is related to sexual risk and substance use among 18–24 year olds. Females (70) and males (56) completed the Sexual Discounting Task, which assessed their likelihood of having unprotected immediate sex versus waiting for sex with a condom, at various delays, with 4 hypothetical sexual partners selected from photographs: the person they most wanted to have sex with, least wanted to have sex with, judged most likely to have a sexually transmitted infection (STI), and judged least likely to have an STI. They also completed instruments assessing HIV knowledge, sexual behaviors, substance use, risk attitudes, inhibition, impulsivity, and sensation-seeking. Condom use likelihood generally decreased with increasing delay. Preference for immediate, unprotected sex was greater for partners whom participants most (vs. least) wanted to have sex with and judged least (vs. most) likely to have an STI. Preference for immediate, unprotected sex in the “most want to have sex with” and “least likely to have an STI” conditions was related to greater lifetime risky sexual partners, lifetime number of unique substances used, disregard of social approval/danger, disinhibition, and sensation/excitement-seeking. Males showed greater likelihood of unprotected sex than females when condom use was undelayed, but delay similarly affected condom use between sexes. Delay discounting should be considered in strategies to minimize youth risk behavior. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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  • Contextual influences on subjective and behavioral responses to alcohol.
    Differential sensitivity to alcohol effects (e.g., increased stimulation and decreased sedation) is associated with heavier use and problems. Although genetic factors contribute to alcohol response (AR), environmental factors may also play a role. This study examined effects of physical context on AR using a between subjects placebo-controlled design. There were 157 (57% male) participants (ages 21–30) who were randomized to 1 of 4 conditions based on beverage (placebo or alcohol [target BrAC = .08 g%]) and physical context (simulated bar or traditional lab). AR was assessed using the Subjective Effects of Alcohol Scale and the Biphasic Alcohol Effects Scale, as well as behavioral tasks including the Balloon Analogue Risk Task (BART) and its negative reinforcement counterpart (MRBURNS). A beverage condition by context interaction emerged for low arousal positive subjective response (SR), and among women, for performance on the BART task. In the lab context only, alcohol (relative to placebo) was associated with stronger low arousal positive SR and, for women, with impaired performance on the BART task. This suggests that a less stimulating lab context may be better suited to differentiating positive alcohol effects from expectancies, whereas a bar context may be better suited to detecting expectancy effects. The findings also suggest that the ability to better appreciate positive alcohol effects (relative to expectations) in less stimulating contexts may lead to a strengthening of these effects among individuals who drink in these environments. (PsycINFO Database Record (c) 2015 APA, all rights reserved)
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