In a work unlike anything she's written before, National Book Award winner Joyce Carol Oates unveils a poignant, intimate memoir about the unexpected death of her husband of forty-six years and its wrenching, surprising aftermath.

"My husband died, my life collapsed."

On a February morning in 2008, Joyce Carol Oates drove her ailing husband, Raymond Smith, to the emergency room of the Princeton Medical Center where he was diagnosed with pneumonia. Both Joyce and Ray expected him to be released in a day or two. But in less than a week, even as Joyce was preparing for his discharge, Ray died from a virulent hospital-acquired infection, and Joyce was suddenly faced—totally unprepared—with the stunning reality of widowhood.

A Widow's Story illuminates one woman's struggle to comprehend a life without the partnership that had sustained and defined her for nearly half a century. As never before, Joyce Carol Oates shares the derangement of denial, the anguish of loss, the disorientation of the survivor amid a nightmare of "death-duties," and the solace of friendship. She writes unflinchingly of the experience of grief—the almost unbearable suspense of the hospital vigil, the treacherous "pools" of memory that surround us, the vocabulary of illness, the absurdities of commercialized forms of mourning. Here is a frank acknowledgment of the widow's desperation—only gradually yielding to the recognition that "this is my life now."

Enlivened by the piercing vision, acute perception, and mordant humor that are the hallmarks of the work of Joyce Carol Oates, this moving tale of life and death, love and grief, offers a candid, never-before-glimpsed view of the acclaimed author and fiercely private woman.

Elizabeth Wurtzel published her memoir of depression, Prozac Nation, to astonishing literary acclaim. A cultural phenomenon by age twenty-six, she had fame, money, respecteverything she had always wanted except that one, true thing: happiness.

For all of her professional success, Wurtzel felt like a failure. She had lost friends and lovers, every magazine job she'd held, and way too much weight. She couldn't write, and her second book was past due. But when her doctor prescribed Ritalin to help her focus-and boost the effects of her antidepressants -- Wurtzel was spared. The Ritalin worked. And worked. The pills became her sugar...the sweetness in the days that have none. Soon she began grinding up the Ritalin and snorting it. Then came the cocaine, then more Ritalin, then more cocaine. Then I need more. I always need more. For all of my life I have needed more...

More, Now, Again is the brutally honest, often painful account of Wurtzel's descent into drug addiction. It is also a love story: How Wurtzel managed to break free of her relationship with Ritalin and learned to love life, and herself, is at the heart of this ultimately uplifting memoir that no reader will soon forget.

Author: Elizabeth Wurtzel
Paperback: 336 pages Bargain Price
Company: Simon & Schuster (2002-12-31)
List Price: $15.00
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The extraordinary story of the artists who propelled themselves to international fame in 1960s Los Angeles

Los Angeles, 1960: There was no modern art museum and there were few galleries, which is exactly what a number of daring young artists liked about it, among them Ed Ruscha, David Hockney, Robert Irwin, Bruce Nauman, Judy Chicago and John Baldessari. Freedom from an established way of seeing, making, and marketing art fueled their creativity, which in turn inspired the city. Today Los Angeles has four museums dedicated to contemporary art, around one hundred galleries, and thousands of artists. Here, at last, is the book that tells the saga of how the scene came into being, why a prevailing Los Angeles permissiveness, 1960s-style, spawned countless innovations, including Andy Warhol's first exhibition, Marcel Duchamp's first retrospective, Frank Gehry's mind-bending architecture, Rudi Gernreich's topless bathing suit, Dennis Hopper's Easy Rider, even the Beach Boys, the Byrds, the Doors, and other purveyors of a California style. In the 1960s, Los Angeles was the epicenter of cool.

Every great joke has a punch line, and every great humor writer has an arsenal of experiences, anecdotes, and obsessions that were the inspiration for that humor. In fact, those who make a career out of entertaining strangers with words are a notoriously intelligent and quirky lot. And boy, do they have some stories.

In this entertaining and inspirational book, you'll hear from 21 top humor writers as they discuss the comedy-writing process, their influences, their likes and dislikes, and their experiences in the industry. You?ll also learn some less useful but equally amusing things, such as:How screenwriter Buck Henry came up with the famous ?plastics? line for The Graduate.How many times the cops were called on co-writers Sacha Baron Cohen and Dan Mazer during the shooting of Borat.What David Sedaris thinks of his critics. What creator Paul Feig thinks would have happened to the Freaks & Geeks crew if the show had had another season.What Jack Handey considers his favorite ?Deep Thoughts.? How Todd Hanson and the staff of The Onion managed to face the aftermath of 9/11 with the perfect dose of humor.How Stephen Merchant and Ricky Gervais created the original version of The Office. What it?s really like in the writers? room at SNL.Funny and informative, And Here's the Kicker is a must-have resource - whether you?re an aspiring humor writer, a fan of the genre, or someone who just likes to laugh.

Author: Mike Sacks
Paperback: 350 pages
Company: Writers Digest Books (2009-07-08)
ISBN: 1582975051
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Although a tremendous body of data has been gathered on the neurochemical changes engendered by exposure to drugs of abuse, the cellular mechanisms responsible for the changes remains unclear. In The Neurochemistry of Drugs of Abuse Syed F. Ali and his co-authors examine the cellular and molecular mechanisms of drugs of abuse (such as cocaine and substituted amphetamines) as well as drugs that have been proposed for the treatment of drug addiction (such as ibogaine, phenyltropane, and phentermine-fenfluramine).

Among the contributors, FDA researchers present the clinical aspect in the development of medications designed to treat drug addiction. Other chapters are devoted to the underlying mechanisms of drug addiction, such as gene expression/molecular mechanisms, medication development, free-radical induced neurotoxicity, and specific neuronal markers.

Bringing together both clinical and basic scientists in a multidisciplinary and multinational forum, The Neurochemistry of Drugs of Abuse presents a significant exchange of ideas in this expanding field of research.

What drives the drug trade, and how has it come to be what it is today? A global history of the acquisition of progressively more potent means of altering ordinary waking consciousness, this book is the first to provide the big picture of the discovery, interchange, and exploitation of the planet's psychoactive resources, from tea and kola to opiates and amphetamines.

Interspersed with notes, correspondence, and transcriptions that catalog a relationship based on curiosity and fear, The Visible Man touches on all of Chuck Klosterman’s favorite themes—the consequence of culture, the influence of media, the complexity of voyeurism, and the existential contradiction of normalcy. Is this comedy, criticism, or horror? Not even Y__ seems to know for sure.

Author: Chuck Klosterman
Hardcover: 240 pages
Company: Scribner (2011-10-04) (2011-10-04)
ISBN: 1439184461
List Price: $25.00
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Critics across the country have raved about Joyce Carol Oates’s ground-breaking memoir A Widow’s Story, lauding its blazing honesty and raw emotion, calling it “immensely moving,” “searing,” “enthralling,” “brave,” “slyly mordant,” and “astonishingly candid.”

On a February morning in 2008, Joyce Carol Oates drove her ailing husband, Raymond Smith, to the emergency room of the Princeton Medical Center, where he was diagnosed with pneumonia. In less than a week, Ray died from a hospital-acquired virulent infection—and Joyce was suddenly faced with the stunning reality of widowhood.

A Widow’s Story illuminates one woman’s struggle to comprehend a life absent of the partnership that had sustained and defined her for nearly half a century. As never before, Joyce Carol Oates shares the derangement of denial, the anguish of loss, the disorientation of the survivor amid a nightmare of “death duties,” and the solace of friendship. Here is a frank acknowledgment of the widow’s desperation—only gradually yielding to the recognition that “this is my life now.”

Enlivened by the piercing vision, acute perception, and mordant humor that are the hallmarks of the work of Joyce Carol Oates, this moving tale of life and death, love and grief, offers a candid, never-before-glimpsed view of this acclaimed author and fiercely private woman.

The precise neurochemical mechanisms underlying this drug-induced neurotoxicity remain unclear. This volume explores this question, specifically addressing the following aspects: (1) the role of genomics and proteomics in drug-induced neurotoxicity, (2) drugs of abuse and medication development, (3) molecular biology and free radicals in drug-induced neurotoxicity, (4) substituted amphetamine-induced neurochemical changes and relationship to neurotoxicity, (5) drugs of abuse and imaging brain structure and function.

NOTE: Annals volumes are available for sale as individual books or as a journal. For information on institutional journal subscriptions, please visit www.blackwellpublishing.com/nyas.

ACADEMY MEMBERS: Please contact the New York Academy of Sciences directly to place your order (www.nyas.org). Members of the New York Academy of Science receive full-text access to the Annals online and discounts on print volumes. Please visit http://www.nyas.org/MemberCenter/Join.aspx for more information about becoming a member

Paperback: 552 pages
Company: Wiley-Blackwell (2006-08-31)
ISBN: 1573316296
List Price: $154.95
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Neurochem Int. 2012 Jan 28;
Del Pilar Escobar A, Cornejo FA, Andrés ME, Fuentealba JA

The effects after the acute activation of the kappa opioid receptor (KOR) can be distinguished from the effect after repeated administration of KOR agonist. Here, we report the effect of repeated administration of U69593 during abstinence after amphetamine-induced locomotor sensitization. Rats were injected once daily with amphetamine for five consecutive days. From day6 to 9, rats that developed locomotor sensitization, received once daily injection of U69593 or vehicle. On day10, all rats were injected with a challenging dose of amphetamine and locomotor activity was measured to assess the expression of sensitization. Microdialysis studies were carried out to assess dopamine extracellular levels in NAc. Rats that develop and express horizontal locomotor sensitization to amphetamine show increased dopamine release in the NAc induced by high K(+). The repeated treatment with U69593 reverses the sensitized depolarization-stimulated dopamine release in the NAc, but not the expression of locomotor sensitization induced by amphetamine. Thus, repeated activation of KORs during early amphetamine withdrawal dissociates the behavioral responses and the neurochemical responses that accompany the expression of sensitization to amphetamine.

Peptides. 2012 Jan; 33(1): 156-63
Kotlinska JH, Gibula-Bruzda E, Koltunowska D, Raoof H, Suder P, Silberring J

Many data indicate that endogenous opioid system is involved in amphetamine-induced behavior. Neuropeptide FF (NPFF) possesses opioid-modulating properties. The aim of the present study was to determine whether pharmacological modulation of NPFF receptors modify the expression of amphetamine-induced conditioned place preference (CPP) and amphetamine withdrawal anxiety-like behavior, both processes relevant to drug addiction/abuse. Intracerebroventricular (i.c.v.) injection of NPFF (5, 10, and 20nmol) inhibited the expression of amphetamine CPP at the doses of 10 and 20nmol. RF9, the NPFF receptors antagonist, reversed inhibitory effect of NPFF (20nmol, i.c.v.) at the doses of 10 and 20nmol and did not show any effect in amphetamine- and saline conditioned rats. Anxiety-like effect of amphetamine withdrawal was measured 24h after the last (14 days) amphetamine (2.5mg/kg, i.p.) treatment in the elevated plus-maze test. Amphetamine withdrawal decreased the percent of time spent by rats in the open arms and the percent of open arms entries. RF9 (5, 10, and 20nmol, i.c.v.) significantly reversed these anxiety-like effects of amphetamine withdrawal and elevated the percent of time spent by rats in open arms at doses of 5 and 10nmol, and the percent of open arms entries in all doses used. NPFF (20nmol) pretreatment inhibited the effect of RF9 (10nmol). Our results indicated that stimulation or inhibition of NPFF receptors decrease the expression of amphetamine CPP and amphetamine withdrawal anxiety, respectively. These findings may have implications for a better understanding of the processes involved in amphetamine dependence.

Neuroscience. 2012 Feb 17; 203: 108-21
Lapish CC, Chiang J, Wang JZ, Phillips AG

Repeated injections of psychostimulants, such as d-amphetamine (d-AMPH), provide a well-validated model of progressive cellular and systems-level alterations in brain function and behavior associated with addiction. The present study employed quantitative measures of both power spectral density and synchrony from local field potentials (LFPs) recorded simultaneously from the prefrontal cortex (PFC), parietal cortex (PAR), and hippocampus (HPC) in awake, behaving rats to assess changes in oscillations during different stages of d-AMPH-induced sensitization. The induction and development of sensitization altered the power of multiple frequency bands in a brain region-specific manner, whereas no changes were observed in animals treated with chronic saline. Specifically, the induction of sensitization to d-AMPH was accompanied by alterations in delta (2-5 Hz) and theta (5-11 Hz) oscillations similar to those observed in EEG recordings from addicted individuals describing craving and hedonic experience of the drug. Sensitization was also related to increased theta coherence between the PFC and HPC, along with suppression of cross-frequency correlations between theta and fast-gamma (65-100 Hz) in both the HPC and the PFC. Collectively, the present findings indicated the induction of a state in which the timing and synchronizing effects of oscillations are altered by sensitization to d-AMPH and are especially pronounced in the PFC. Furthermore, numerous LFP-derived measures were characterized that may serve as objective physiological correlates of pathological states observed in addiction.

Neurobiol Learn Mem. 2011 Dec 16;
Grégoire S, Rivalan M, Le Moine C, Dellu-Hagedorn F

Concomitant deficits in working memory and behavioral inhibition in several psychiatric disorders like attention-deficit/hyperactivity disorder, addiction or mania, suggest that common brain mechanisms may underlie their etiologies. Based on the theoretical assumption that a continuum exists between health and mental disorders, we explored the relationship between working memory and inhibition in healthy individuals, through spontaneous inter individual differences in behavior, and tested the hypothesis of a functional link through the fronto-striatal dopaminergic system. Rats were classified into three groups, showing good, intermediate and poor working memory and were compared for their inhibitory abilities. These two functions were simultaneously modulated by a dose-effect of d-amphetamine and in situ hybridization was used to quantify dopaminergic receptor (RD1) mRNAs in prefrontal cortex and striatal areas. A functional relationship between working memory and inhibition abilities was revealed. Both functions were similarly modulated by d-amphetamine according to an inverted-U shaped relationship and depending on initial individual performances. D-amphetamine selectively improved working memory and inhibition of poor and intermediate performers at low doses whereas it impaired both processes in good performers at a higher dose. D1 receptors were less expressed in prelimbic, infralimbic and anterior cingulate cortices of good compared to intermediate and poor performers, whereas no difference was observed between groups in striatal areas. The synergy of working memory and inhibitory abilities, observed in both healthy and psychiatric populations, may originate from endogenous variability in dopaminergic prefrontal cortex activity. Such findings confirm the validity of a dimensional approach, based on the concept of continuity between health and mental disorders for identifying endophenotypes of mental disorders.

Emerg Nurse. 2011 Oct; 19(6): 16-9; quiz 21
North J

This article discusses the origins of illegally produced methamphetamine, its use worldwide and its growing popularity in the UK. It also discusses the drug's effects on users, the possible treatment options and the burden that increased use of methamphetamine will place on emergency departments in the UK.

Rev Med Liege. 2011 Oct; 66(10): 540-4
Bertrand X, Gensburger M, Steckx E

Mephedrone is a designer drug recently appeared on the belgian market of the drugs of misuse. The aim of this journal paper is to provide a review on the available data about mephedrone and to call the attention of the first line practitioners who will have to face this emerging problem.

Biol Psychiatry. 2011 Dec 29;
Anker JJ, Brimijoin S, Gao Y, Geng L, Zlebnik NE, Parks RJ, Carroll ME

BACKGROUND: Cocaine dependence is a pervasive disorder with high rates of relapse. In a previous study, direct administration of a quadruple mutant albumin-fused butyrylcholinesterase that efficiently catalyzes hydrolysis of cocaine to benzoic acid and ecgonine methyl ester acutely blocked cocaine seeking in an animal model of relapse. In the present experiments, these results were extended to achieve a long-duration blockade of cocaine seeking with a gene transfer paradigm using a related butyrylcholinesterase-based cocaine hydrolase (CocH). METHODS: Male and female rats were allowed to self-administer cocaine under a fixed-ratio 1 schedule of reinforcement for approximately 14 days. Following the final self-administration session, rats were injected with CocH vector or a control injection (empty vector or saline), and their cocaine solutions were replaced with saline for 14 days to allow for extinction of lever pressing. Subsequently, they were tested for drug-primed reinstatement by administering intraperitoneal injections of saline (S), cocaine (C) (5, 10, and 15 mg/kg), and d-amphetamine according to the following sequence: S, C, S, C, S, C, S, d-amphetamine. Rats then received cocaine-priming injections once weekly for 4 weeks and, subsequently, once monthly for up to 6 months. RESULTS: Administration of CocH vector produced substantial and sustained CocH activity in plasma that corresponded with diminished cocaine-induced (but not amphetamine-induced) reinstatement responding for up to 6 months following treatment (compared with high-responding control animals). CONCLUSIONS: These results demonstrate that viral transfer of CocH may be useful in promoting long-term resistance to relapse to cocaine addiction.

Addiction. 2011 Nov 30;
Humeniuk R, Ali R, Babor T, Souza-Formigoni ML, de Lacerda RB, Ling W, McRee B, Newcombe D, Pal H, Poznyak V, Simon S, Vendetti J

Aims.  This study evaluated the effectiveness of a brief intervention (BI) for illicit drugs (cannabis, cocaine, amphetamine-type stimulants and opioids) linked to the WHO Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The ASSIST screens for problem or risky use of 10 psychoactive substances,producing a score for each substance that falls into either a 'low', 'moderate' or 'high' risk category. Design.  Prospective, randomized controlled trial in which participants were either assigned to a 3-month wait-list control condition or received brief motivational counseling lasting an average of 13.8 minutes for the drug receiving the highest ASSIST score. Setting.  Primary health care settings in four countries: Australia, Brazil, India and the United States of America. Participants.  731 males and females scoring within the moderate risk range of the ASSIST for cannabis, cocaine, amphetamine-type stimulants, or opioids. Measurements.  ASSIST Specific Substance Involvement Scores for cannabis, stimulants or opioids, and, ASSIST Total Illicit Substance Involvement Score at baseline and 3 months post randomization. Findings.  Omnibus analyses indicated that those receiving the BI had significantly reduced scores for all measures, compared with control participants. Country-specific analyses showed that, with the exception of the site in the United States, BI participants had significantly lower ASSIST Total Illicit Substance Involvement scores at follow-up compared with the control participants. The sites in India and Brazil demonstrated a very strong brief intervention effect for Cannabis Scores (p < 0.005 for both sites); as did the sites in Australia (p < 0.005) and Brazil (p < 0.05) for Stimulant Scores, and the Indian site for Opioid Scores (p < 0.01). Conclusions.  The ASSIST-linked brief intervention aimed at reducing illicit substance use and related risks is effective at least in the short-term, and the effect generalises across countries.

J Psychosoc Nurs Ment Health Serv. 2011 Nov; 49(11): 7

J Med Toxicol. 2011 Nov 23;
Prosser JM, Nelson LS

Synthetic cathinones have recently emerged and grown to be popular drugs of abuse. Their dramatic increase has resulted in part from sensationalized media attention as well as widespread availability on the Internet. They are often considered "legal highs" and sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. Cathinone is a naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are derivatives of this compound. Those that are being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone. Synthetic cathinones are phenylalkylamines derivatives, and are often termed "bk-amphetamines" for the beta-ketone moiety. They may possess both amphetamine-like properties and the ability to modulate serotonin, causing distinct psychoactive effects. Desired effects reported by users of synthetic cathinones include increased energy, empathy, openness, and increased libido. Cardiac, psychiatric, and neurological signs and symptoms are the most common adverse effects reported in synthetic cathinone users who require medical care. Deaths associated with use of these compounds have been reported. Exposure to and use of synthetic cathinones are becoming increasingly popular despite a lack of scientific research and understanding of the potential harms of these substances. The clinical similarities to amphetamines and MDMA specifically are predictable based on the chemical structure of this class of agents. More work is necessary to understand the mechanisms of action, toxicokinetics, toxicodynamics, metabolism, clinical and psychological effects as well as the potential for addiction and withdrawal of these agents.

Lancet. 2012 Jan 7; 379(9810): 55-70
Degenhardt L, Hall W

This paper summarises data for the prevalence, correlates, and probable adverse health consequences of problem use of amphetamines, cannabis, cocaine, and opioids. We discuss findings from systematic reviews of the prevalence of illicit drug use and dependence, remission from dependence, and mortality in illicit drug users, and evidence for acute and chronic effects of illicit drug use. We outline the regional and global distribution of use and estimated health burden from illicit drugs. These distributions are likely to be underestimates because they have not included all adverse outcomes of drug use and exclude those of cannabis--the mostly widely used illicit drug. In high-income countries, illicit drug use contributes less to the burden of disease than does tobacco but a substantial proportion of that due to alcohol. The major adverse health effects of cannabis use are dependence and probably psychotic disorders and other mental disorders. The health-related harms of cannabis use differ from those of amphetamine, cocaine, and opioid use, in that cannabis contributes little to mortality. Intelligent policy responses to drug problems need better data for the prevalence of different types of illicit drug use and the harms that their use causes globally. This need is especially urgent in high-income countries with substantial rates of illicit drug use and in low-income and middle-income countries close to illicit drug production areas.

Psychopharmacology (Berl). 2012 Jan; 219(2): 313-26
Baarendse PJ, Vanderschuren LJ

High levels of impulsivity are a core symptom of psychiatric disorders such as ADHD, mania, personality disorders and drug addiction. The effectiveness of drugs targeting dopamine (DA), noradrenaline (NA) and/or serotonin (5-HT) in the treatment of impulse control disorders emphasizes the role of monoaminergic neurotransmission in impulsivity. However, impulsive behavior is behaviorally and neurally heterogeneous, and several caveats remain in our understanding of the role of monoamines in impulse control.This study aims to investigate the role of DA, NA and 5-HT in two main behavioral dimensions of impulsivity.The effects of selective DA (GBR12909; 2.5-10 mg/kg), NA (atomoxetine; 0.3-3.0 mg/kg) and 5-HT (citalopram; 0.3-3.0 mg/kg) reuptake inhibitors as well as amphetamine (0.25-1.0 mg/kg) were evaluated on impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task (DRT). In the 5-CSRTT, neuropharmacological challenges were performed under baseline and long intertrial interval (ITI) conditions to enhance impulsive behavior in the task.Amphetamine and GBR12909 increased impulsive action and perseverative responding and decreased accuracy and response latency in the 5-CSRTT. Atomoxetine increased errors of omission and response latency under baseline conditions in the 5-CSRTT. Under a long ITI, atomoxetine also reduced premature and perseverative responding and increased accuracy. Citalopram improved impulse control in the 5-CSRTT. Amphetamine and GBR12909, but not citalopram or atomoxetine, reduced impulsive choice in the DRT.Elevation of DA neurotransmission increases impulsive action and reduces impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive action.

Psychopharmacology (Berl). 2012 Jan 31;
Richtand NM, Ahlbrand R, Horn PS, Chambers B, Davis J, Benoit S

RATIONALE: Addiction is a disease of learning and memory, as learning processes underlying acquisition, extinction, and reinstatement of drug-paired associations play central roles in addiction. Early developmental stress enhances risk for drug problems in adulthood. Environmental factors influencing learning and memory processes relevant to addiction remain incompletely characterized. OBJECTIVES: To determine effects of prenatal immune activation and developmental stress on conditioned place preference to amphetamine, and reversal learning. METHODS: Pregnant Sprague-Dawley rats were injected with polyinosinic:polycytidylic acid (poly I:C) or vehicle on gestational day 14. Half of the male offspring received 2 h of restraint stress at post-natal day 35. Behavioral testing was performed in adulthood. RESULTS: Restraint stress inhibited acquisition of place preference to low-dose amphetamine (0.5 mg/kg), while poly I:C treatment had no measurable effect on place preference acquisition. In contrast, drug-induced reinstatement of preference for drug-paired chamber was enhanced in offspring of poly I:C-treated dams [F(1,25) = 5.31, p = 0.03]. Performance on a Morris water maze reversal learning task was impaired in poly I:C offspring. Reversal learning performance was correlated with place preference reinstatement in non-stressed (r (2) = 0.42, p = 0.0095), but not stressed rats (r (2) =0.04, p = 0.49). CONCLUSIONS: Prenatal immune activation enhances drug-induced reinstatement of conditioned place preference. These data demonstrate longstanding impact on behaviors with potential influence on risk for drug relapse as a consequence of prenatal immune activation. Further study is needed to determine clinical and epidemiological consequences of similar exposures in human populations.

Pharmacol Biochem Behav. 2012 Jan 20;
Sadananda M, Natusch C, Karrenbauer B, Schwarting RK

In recent years, 50-kHz ultrasonic vocalizations of laboratory rats have become increasingly important behavioral measures in research on emotion and motivation, since these calls may help to study appetitive subjective states, for example in relation to addiction. Among others, 50-kHz calls occur when rats experience or expect rewards, including drugs of abuse, and it is assumed that these calls depend on dopamine function, especially in the meso-limbic system. One established means to induce 50-kHz calls is to challenge rats with d-amphetamine, a psychomotor stimulant, which acts largely by boosting dopamine and noradrenaline function in the brain. In a 1st experiment, we studied whether another psycho-stimulatory amphetamine, namely the derivative 3,4-methylene-dioxymethamphetamine (MDMA, Ecstasy), could also enhance 50-kHz calls by using an activity box and testing conditions, which had previously been found to be appropriate in case of d-amphetamine. In support of previous work, we found that MDMA (2.5, 5, 10mg/kg, ip) dose-dependently increased locomotion and center time, together with decreases in rearing activity, but the drug did not elicit 50-kHz calls. Assuming that this lack of effect is due to the drug's substantial pro-serotonergic effects in the brain, which may inhibit 50-kHz calls, we performed a 2nd experiment where we tested the serotonin 5-HT(1A) receptor agonist 8-hydroxy-2-tetralin (8-OH-DPAT; 0.05, 0.5, 2.5mg/kg, ip). This drug dose-dependently stimulates serotonin autoreceptors and heteroreceptors, can act in a psycho-stimulatory way and can enhance dopamine function. In the activity box, 8-OH-DPAT increased locomotor activity (0.5, 2.5mg/kg) and decreased rearing (2.5mg/kg); that is, the drug seemed to share some psycho-stimulatory effects with MDMA. Unlike MDMA, 8-OH-DPAT enhanced 50-kHz calls in a dose-dependent way, namely only with the 0.5mg/kg dose. These results are discussed with respect to their possible neurochemical mechanisms, especially on 5-HT and dopamine in the brain.

J Pak Med Assoc. 2011 Jun; 61(6): 566-71
Shamshiri Milani H, Abadi AR, Helmzadeh Z, Abachizadeh K

To determine prevalence of ecstasy use and its predisposing factors among Iranian high school female students in Tehran, capital of Iran.In this cross-sectional study, 2350 female students of 36 high schools from Tehran, were selected by multi-stage cluster sampling to determine prevalence of ecstasy use and its predisposing factors. SPSS- version 13 was employed to conduct analysis through chi-square, fisher's exact test and logistic regression methods.The prevalence of ecstasy use was 2.3% (95% CI: 1.7-2.9%). Party was the most prevalent place of first use (65%) and access was easy for most users (63%). In multivariate analysis, smoking (P-V = 0.005), alcohol use (P-V = 003), use of other substances (P-V < 0.001), being in relationship with boys (P-V = 0.015), families without one or two parents (P-V = 0.020), night spending at friends home without parents' permission (P-V = 0.001) were associated with ecstasy use.Due to relation of ecstasy use with other substances, designed programmes should be comprehensive, with different strategies and collaboration of several sectors. The main strategies are to improve students' health literacy, family support, to limit supply and access, and to legislate appropriate regulatory laws.

Lakartidningen. 2011 Oct 9-15; 108(45): 2304-7
Franck J

Addict Biol. 2011 Nov 29;
Childs E, de Wit H

Learned associations between drugs and the places they are used are critical to the development of drug addiction. Contextual conditioning has long been studied in animals as an indirect measure of drug reward, but little is known about the process in humans. Here, we investigated de novo contextual conditioning with d-amphetamine in healthy humans (n = 34). Volunteers underwent four conditioning sessions conducted in two testing rooms with double-blind, alternating d-amphetamine (20 mg) and placebo administration. Before conditioning procedures began, they rated the two rooms to examine pre-existing preferences. One group (Paired, n = 19) always received d-amphetamine in their least preferred room and placebo in the other during conditioning sessions. Another group (Unpaired, n = 15) received d-amphetamine and placebo in both rooms. Subjective drug effects were monitored at repeated times. At a separate re-exposure test, preference ratings for the drug-associated room were increased among the Paired group only, and more subjects in the Paired than the Unpaired group switched their preference to their initially least preferred room. Also, ratings of d-amphetamine drug liking independently predicted room liking at test among the Paired group only. Further, Paired group subjects reported greater stimulation and drug craving after d-amphetamine on the second administration, relative to the first. This study supports preliminary findings that humans, like animals, develop a preference for a place associated with d-amphetamine that is related to its subjective effects. These findings also suggest that experiencing d-amphetamine in a consistent environment produces context-dependent changes in its subjective effects, including an enhanced rewarding efficacy and abuse potential.

J Psychoactive Drugs. 2011 Sep; Suppl 7: 68-76
Brecht ML, Urada D

Methamphetamine (meth) is a major drug of abuse in California and several other states, particularly among criminal offender populations. Over the past decade, substance abuse treatment systems have had to adapt to and accommodate the increasing needs of meth users and, in California, deal with the impact of Proposition 36, which has resulted in a greater number of criminal offenders entering the treatment system. This study examines selected treatment performance and outcome indicators for California Proposition 36 offenders entering substance abuse treatment for meth use and compares their performance and outcomes to other subgroups of California treatment clients differentiated by whether or not they were admitted to treatment through Proposition 36 and whether or not their primary substance was meth. Significant improvements in all outcome domains were seen across the populations, and treatment performance and outcomes were not substantively inferior for the offender or meth-using groups.

Psychopharmacology (Berl). 2011 Dec 23;
Schwendt M, Sigmon SA, McGinty JF

RATIONALE: Regulator of G-protein signaling 4 (RGS4) is a brain-enriched negative modulator of G-protein-coupled receptor signaling. Decreased availability of RGS4 in the frontal cortex and striatum has been described in animal models of schizophrenia and drug addiction. However, cellular and behavioral consequences of dysregulated RGS4-dependent receptor signaling in the brain remain poorly understood. OBJECTIVE: This study aims to investigate whether RGS4, through inhibiting the function of mGluR5 receptors in the dorsal striatum (dSTR), regulates cellular and behavioral responses to acute amphetamine. METHODS: After herpes simplex virus-RGS4 was infused into the dSTR, RGS4 overexpression as well as binding of recombinant RGS4 to mGluR5 was assessed. The effect of RGS4 overexpression on behavioral activity induced by the intrastriatal mGluR5 agonist, DHPG, or amphetamine was recorded. Activation of extracellular signal-regulated kinase (ERK) and Akt (protein kinase B) was measured in the dSTR tissue at the end of each behavioral experiment. RESULTS: RGS4 overexpressed in the dSTR coimmunoprecipitated with mGluR5 receptors and suppressed both behavioral activity and phospho-ERK levels induced by DHPG. RGS4 overexpression or the mGluR5 antagonist, 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP), attenuated amphetamine-induced phospho-ERK (but not phospho-Akt) levels. RGS4 suppressed amphetamine-induced vertical activity and augmented horizontal activity over 90 min. Similarly, MTEP augmented amphetamine-induced horizontal activity, but did not affect vertical activity. CONCLUSIONS: The present data demonstrate that RGS4 in the dSTR attenuates amphetamine-induced ERK signaling and decreases the behavioral efficacy of acute amphetamine likely by limiting mGluR5 function.

Drug Alcohol Depend. 2012 Jan 30;
Fukushiro DF, Josino FS, Saito LP, Costa JM, Zanlorenci LH, Berro LF, Fernandes-Santos L, Morgado F, Mári-Kawamoto E, Frussa-Filho R

BACKGROUND: Previous studies have demonstrated a preventive effect of continuous environmental enrichment during early development on the vulnerability of rodents to drug addiction-related behaviors. Recently, it was demonstrated that a continuous environmental enrichment could eliminate already established addiction-related behaviors in mice. The present study compared the effects of intermittent or continuous exposure to novel stimuli during repeated amphetamine (Amp) treatment on the development of behavioral sensitization (an animal model of addiction-related neuroadaptations) in adult mice. METHODS: Three-month-old male Swiss mice were treated with 2.5mg/kg Amp every other day for 13 days in their home cages. Novel objects were presented in their home cages for 2h on non-drug treatment days (experiment 1) or for 24h/day during the 13 days of drug treatment (experiment 2). Seven days after the drug treatment had finished, the mice were challenged with 2.5mg/kg Amp, and their locomotor activity was quantified in a familiar open field for 10min. RESULTS: Intermittent exposure to the novel objects did not modify the acute Amp locomotor stimulatory effect but potentiated the development of Amp-induced locomotor sensitization. This enhanced sensitization was due to increased locomotion in the central squares of the apparatus, which suggests anxiolysis or increased impulsiveness. Conversely, continuous exposure to the novel objects potentiated the acute Amp locomotor stimulatory effect and blunted the development of Amp-induced locomotor sensitization. CONCLUSIONS: We conclude that addiction-related behaviors can be differentially and critically modified depending on the schedule and period of the novelty exposure.