Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis.

Despite substantial evidence for sex differences in addiction epidemiology, addiction-relevant behaviors and associated neurobiological phenomena, the mechanisms and implications of these differences remain unknown. Genetic analysis in model organism is a potentially powerful and effective means of discovering the mechanisms that underlie sex differences in addiction. Human genetic studies are beginning to show precise risk variants that influence the mechanisms of addiction but typically lack sufficient power or neurobiological mechanistic access, particularly for the discovery of the mechanisms that underlie sex differences. Our thesis in this review is that genetic variation in model organisms are a promising approach that can complement these investigations to show the biological mechanisms that underlie sex differences in addiction

Sex differences, gender and addiction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134421/1/jnr23963_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134421/2/jnr23963.pd

UK fatalities associated with caffeine : Annex 3

Fatalities due to caffeine are not monitored in the UK. Whilst the National Programme on Substance Abuse Deaths is aware of caffeine being used as a 'cutting' agent in street drugs and 'legal highs' (see also Cole et al, 2011), there seems to have been only a few possible cases in the UK where caffeine may have had a role in causing or contributing to death. None of these cases were reported to np-SAD as they do not meet our case definition. However, through searches of Medline and the Internet it was possible to identify several recent deaths where caffeine was thought to have possibly played a part. These are dealt with by date of inquest

Adolescent D-amphetamine treatment in a rodent model of attention deficit/hyperactivity disorder: impact on cocaine abuse vulnerability in adulthood

RATIONALE: Stimulant medications for attention-deficit/hyperactivity disorder (ADHD) in adolescents remain controversial with respect to later development of cocaine abuse. Past research demonstrated that adolescent methylphenidate treatment increased several aspects of cocaine self-administration during adulthood using the spontaneously hypertensive rat (SHR) model of ADHD. Presently, we determined effects of the alternate stimulant medication, d-amphetamine, on cocaine self-administration. OBJECTIVES: We tested the hypothesis that adolescent d-amphetamine would not increase cocaine self-administration in adult SHR, given that d-amphetamine has a different mechanism of action than methylphenidate. METHODS: A pharmacologically relevant dose of d-amphetamine (0.5 mg/kg) or vehicle was administered throughout adolescence to SHR and two control strains, Wistar-Kyoto (WKY) and Wistar (WIS). Three aspects of cocaine abuse vulnerability were assessed in adulthood after discontinuing adolescent treatments: acquisition rate and dose-related responding under fixed (FR) and progressive (PR) ratio schedules. RESULTS: Adult SHR acquired cocaine self-administration faster and self-administered more cocaine across multiple doses compared to WKY and WIS under FR and PR schedules, indicating that SHR is a reliable animal model of comorbid ADHD and cocaine abuse. Relative to vehicle, SHR and WIS with adolescent d-amphetamine treatment self-administered less cocaine upon reaching acquisition criteria, and WIS additionally acquired cocaine self-administration more slowly and had downward shifts in FR and PR cocaine dose-response curves. WKY with adolescent d-amphetamine treatment acquired cocaine self-administration more quickly relative to vehicle. CONCLUSIONS: In contrast to methylphenidate, adolescent d-amphetamine did not augment cocaine self-administration in SHR. Adolescent d-amphetamine treatment actually protected against cocaine abuse vulnerability in adult SHR and WIS.National Institutes of Health grant DA011716 and the Clara Mayo Memorial Fellowship at Boston University. (DA011716 - National Institutes of Health; Clara Mayo Memorial Fellowship at Boston University)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5026317/Published versio

Individual differences in the neuropsychopathology of addiction.

Drug addiction or substance-use disorder is a chronically relapsing disorder that progresses through binge/intoxication, withdrawal/negative affect and preoccupation/anticipation stages. These stages represent diverse neurobiological mechanisms that are differentially involved in the transition from recreational to compulsive drug use and from positive to negative reinforcement. The progression from recreational to compulsive substance use is associated with downregulation of the brain reward systems and upregulation of the brain stress systems. Individual differences in the neurobiological systems that underlie the processing of reward, incentive salience, habits, stress, pain, and executive function may explain (i) the vulnerability to substance-use disorder; (ii) the diversity of emotional, motivational, and cognitive profiles of individuals with substance-use disorders; and (iii) heterogeneous responses to cognitive and pharmacological treatments. Characterization of the neuropsychological mechanisms that underlie individual differences in addiction-like behaviors is the key to understanding the mechanisms of addiction and development of personalized pharmacotherapy

Importance of Sex Differences in Impulse Control and Addictions

Background Nursing students are expected to deliver holistic care in their upcoming career. Developing spirituality during nursing training is poorly understood. Objectives The current study aimed to explore the process of developing spirituality among Iranian nursing undergraduates. Patients and Methods The study employed Grounded theory approach and purposive sampling with maximum variation to select the participants among undergraduate nursing students in their fourth-year of study in the nursing school of Tehran University of Medical Sciences. Data were gathered through semi structured interviews with nineteen nursing students and one faculty member (n = 20). Strauss and Corbin approach was selected for data analysis. Results Data analysis revealed that developing spirituality during nursing education is an intuitive development including three stages: early frustration, intuitive development through hardship and seeking meaning and fulfilment. This process is influenced by educational/caring environment as well as role models. Conclusions Upbringing capable nurses to deliver spiritual care require supportive environment and influential role models to encourage students’ spiritual development. Developing spiritually may end in delivering spiritual care and provide nursing students with inner strength for better confrontation with serious situations common in their upcoming career

Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature

Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaineseeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals

Sex differences in cocaine use in rats

Les mâles et les femelles répondent différemment à la cocaïne. La transition vers la toxicomanie peut être plus rapide chez les femmes. En préclinique, les femelles sont plus vulnérables aux propriétés renforçantes et motivationnelles de la cocaïne. Les études rapportant des différences sexuelles sur la consommation de cocaïne ont majoritairement été menées avec un accès continu à la drogue [e.g., LgA (sessions de 6 h), Long Access ou ShA (sessions de 1-2 h), Short Access]. Ceci favorise des niveaux de cocaïne au cerveau soutenus pendant toute la session d’auto-administration. Or, les usagers les plus expérimentés de cocaïne consommeraient la drogue par intermittence au sein d’une session d’intoxication, ce qui produirait des pics de cocaïne au cerveau. Un nouveau modèle d’auto-administration de cocaïne chez le rat autorise cet accès intermittent (IntA) à la cocaïne. L’accès IntA, versus LgA, produit les changements neurobiologiques, psychologiques et comportementaux pertinents à la toxicomanie. Ici, nous avons comparé la consommation de cocaïne chez des mâles et des femelles ayant un accès quotidien IntA ou LgA à la drogue (10 sessions de 6 h, 0.25 mg/kg/infusion, i.v.). Les rats des deux sexes LgA ont consommé plus de cocaïne que les rats IntA, mais seules les femelles LgA ont escaladé leur consommation. La sensibilisation psychomotrice était uniquement vue chez les rats IntA, de façon plus importante chez les femelles. Cinq et 25 jours après la dernière session IntA ou LgA, la motivation pour la drogue sous ratio progressif (0.083-0.75 mg/kg/infusion) était similaire chez les rats IntA et LgA. Les femelles étaient plus motivées à avoir la drogue que les mâles, uniquement dans un contexte IntA. Ainsi, les conditions LgA et IntA pourraient être utiles à étudier les différences sexuelles dans la consommation de cocaïne ou dans l’état motivationnel des animaux pour la drogue, respectivement.In both humans and laboratory animals, females and males can respond differently to cocaine. Women can progress more rapidly from initial cocaine use to addiction. Studies in laboratory rodents have also demonstrated that females can be more vulnerable to the reinforcing and incentive motivational effects of cocaine. Most preclinical studies characterizing the effects of cocaine use in females and males have been conducted using continuous-access self-administration procedures [e.g., (6 h sessions), Long Access or ShA (1-2 h sessions), Short Access]. These procedures achieve produces high brain concentrations of drug. However, human addicts take cocaine intermittently during a bout of intoxication, and this would produce spiking brain cocaine levels. A recent intermittent-access (IntA) cocaine self-administration procedure models this in rats. Compared to LgA, IntA self-administration is uniquely effective in producing the neurobiological, psychological and behavioral changes that underlie the transition to cocaine addiction. Here, we compared cocaine use in female and male rats that self-administered the drug (0.25 mg/kg/ infusion, i.v.) during 10 daily, 6-h LgA or IntA sessions. LgA rats took more cocaine than IntA rats, and only female LgA rats escalated their intake. However, only IntA rats (both sexes) developed psychomotor sensitization and sensitization was greatest in the females. Five and 25 days after the last self-administration session, we quantified incentive motivation for cocaine by measuring breakpoints for the drug under progressive ratio under progressive ratio schedule. There were no significant sex differences on this measure in LgA rats. However, under IntA, females reached higher breakpoints for cocaine than males. Thus, LgA might be best suited to study sex differences in cocaine intake, while IntA might be best suited to study sex differences in incentive motivational processes in cocaine addiction

The Effect of Gender and Narcotic or Stimulant Abuse on Drug-Related Locus of Control

Substance use disorders cause significant neurological damage, cognitive impairment, and maladaptive behaviors that negatively affect a person\u27s quality of life. The purpose of this study was to explore the effect gender and primary drugs have on locus of control. Generalized expectancy theory helped to explain the behavior of patients diagnosed with substance use disorders and their inability to control ongoing drug use. The research question focused on to what extent drug-related locus of control scores differ by primary drug (narcotic vs. stimulant), gender (male vs. female), and their interaction. Data measuring locus of control from 553 participants provided a subset of 410 participants who identified narcotics or stimulants as their primary drug. A 2x2 full factorial ANOVA was conducted. The results of this study indicated there is a significant interaction between primary drug use and gender. The results could have positive social change implications for the addiction field because of the value of understanding the interdependency of internal-external thought processes related to drug use, the ability to change stigma associated with addiction and gender, and the value of understanding the need for individualized treatment as locus of control shifts from external to internal. It is recommended that the drug-related locus of control instrument become part of treatment protocol along with evidence-based interventions