Targeted Brain Derived Neurotropic Factors (BDNF) Delivery across the Blood-Brain Barrier for Neuro-Protection Using Magnetic Nano Carriers: An In-Vitro Study

Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effectivein-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.

The effectiveness of female -sensitive substance abuse treatment

This research investigated whether female-sensitive treatment was more effective than a traditional mixed-gender modal. The study participants were evaluated for levels of depression, self-esteem, social support, and presence and severity of addiction. Analyses were conducted to see which demographic, treatment, and service variables were associated with treatment survival rates. It was found that the chemical dependent treatments evaluated all produced equally ineffective results. The women surveyed did have significantly high levels of depression and presence and severity of addiction, yet moderate levels of self-esteem and social support. A mixed-gender chemical dependency model which provided mental health services focusing on depression was recommended. Ancillary services which provided self-esteem building and social support was also suggested. ^

Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers.

Different Wars Require Different Strategies: Separating the “War on Drugs” from the “War on Drug [Traffickers]”

Using the securitization framework to highlight the arguments that facilitated the “War on Drugs”, this paper highlights a separate war against drug traffickers. Facilitated by ideology through the rhetoric promoted by the “War on Drugs,” the fear of communist expansion and democratic contraction, the “War on Drug Traffickers” was implemented, requiring its own strategy separate from the “War on Drugs.” This is an important distinction because the play on words changes the perception of the issue from one of drug addiction to one of weak institutions and insurgent/terrorist threat to those institutions. Furthermore, one cannot propose strategy to win, lose, or retreat in a war that one has been unable to identify properly. And while the all-encompassing “War on Drugs” has motivated tremendous discourse on its failure and possible solutions to remedy its failure, the generalizations made as a result of the inability to distinguish between the policies behind drug addiction and the militarized policies behind drug trafficking have discounted the effect of violence perpetrated by the state, the rationale for the state perpetrating that violence, and the dependence that the state has on foreign actors to perpetrate such violence. This makes it impossible to not only propose effective strategy but also to persuade states that participate in the “War on Drug Traffickers” to adopt the proposed strategy.

Nec(Romantic)

NEC(ROMANTIC) is a poetry collection thematically linked through images of insects, celestial bodies, bones, and other elements of the supernatural. These images are indicative of spells, but the parenthesis around romantic in the collection’s title also implies idealism. The poems explore the author’s experiences with death, grief, love, oppression, and addiction. NEC(ROMANTIC) employs the use of traditional forms such as the villanelle, sestina, and haiku to organize these experiences. Prose poetry and a peca kucha ground the center of NEC(ROMANTIC) which alternates between lyrical and narrative gestures. NEC(ROMANTIC) is influenced by Sylvia Plath. The author uses Plath’s methods of compression, sound, and rhythm to create a swift, child-like tone when examining emotionally laden topics. Ilya Kaminsky influences lyrical elements of the poems, including surrealism. Spencer Reese’s combination of the natural and personal world is also paramount to this book. Adrienne Rich and Audre Lorde influence NEC(ROMANTIC)’s political poetry.

Non-prescription medicine misuse, abuse and dependence : a cross-sectional survey of the UK general population

This study was supported by the Society of the Study of Addiction in the form of a PhD studentship awarded to NF.

Avaliação das Funções Executivas em Dependentes Químicos

The aim of this study was to investigate possible alterations in attentive functions and mental flexibility in individuals diagnosed with Addiction. The sample (n=40) was located for convenience, and included 20 individuals with addiction behaviors (G1), and 20 individuals who do not use harmfully psychoactive substances (G2). Assessment instruments used were: Experimental and Computerized Test of Continuous Performance, and the Wisconsin Card Sorting Test. It was concluded that individuals in the G1 group had a poorer performance in all categories analyzed on the Wisconsin Card Sorting Test and in reaction time on the Experimental and Computerized Test (p<0,05), showing a deficit in mental flexibility and attentive functions, which may have direct implications on addictive behaviors and treatment.

Doing Research with Vulnerable Populations: The Case of Intravenous Drug Users

Article

Investigating the developmental and behavioral consequences of maternal immune activation on affected offspring

Maternal infection during pregnancy increases the risk of several neuropsychiatric disorders later in life, many of which have a component of dopaminergic (DA) dysfunction, including schizophrenia, autism spectrum disorders (ASD), and attention deficit hyperactivity disorder (ADHD). The majority of DA neurons are found in the adult midbrain; as such the midbrain is a key region of interest regarding these disorders. The literature is conflicting regarding the behavioral alterations following maternal immune activation (MIA) exposure, and the cellular and molecular consequences of MIA on the developing midbrain remain to be fully elucidated. Thus, this thesis aimed to establish the consequences of acute and mild MIA on offspring dopamine-related behaviors, as well as the associated cellular and molecular disturbances of MIA on offspring midbrains. We utilized a rat model of MIA using low dose (50μg/kg, I.P.) of LPS administered at different gestational ages. Our first study indicated that MIA at later gestational ages significantly increased pro-inflammatory IL-1β expression, and reduced HSD11B2 expression in the placenta, which is an important regulator of fetal development. In utero LPS exposure at later gestational ages also impaired the growth of neurons from affected offspring. This study identified key gestational stages during which MIA resulted in differential effects. We utilized these time points in subsequent studies, the next of which investigated neurobehavioral outcomes following MIA. Our results from that study showed that motor differences occurred in juvenile offspring following MIA at E16 only, and these differences were compensated for in adolescence. Then, there was a decline in motor behavior capabilities in adulthood, again only for animals exposed to MIA on E16 (and not E12). Furthermore, our results also demonstrated adolescent and adult offspring that were exposed to MIA at E12 had diminished responses to amphetamine in reward seeking behaviors. In our final study, we aimed to investigate the molecular and cellular changes following MIA which might explain these behavioral alterations. This final study showed a differential inflammatory response in fetal midbrains depending on gestational age of exposure as well as differential developmental alterations. For example, LPS exposure at E16 resulted in decreased VM neurosphere size after 7DIV and this was associated with an increased susceptibility to neurotoxic effects of pro-inflammatory cytokines for VM neurospheres and VM DA neurons treated in culture. In utero LPS exposure at E16 also reduced DA neuron count of fetal VM, measured by TH staining. However, there were no differences in DA neuron number in juvenile, adolescent, or adult offspring. Similarly, LPS exposure did not alter cell number or morphology of glial cells in the midbrains of affected offspring. In conclusion, this thesis indicated later rat pregnancy (E16) as vulnerable time for MIA to affect the development of the nigrostriatal pathway and subsequent behavioral outcomes, possibly implicating a role for MIA in increased risk for disorders associated with motor behavior, like PD. These effects may be mediated through alterations in the placenta and altered inflammatory mediators in the offspring brain. This thesis has also shown that MIA in earlier rat pregnancy (E12) results in altered mesocorticolimbic function, and in particular MIA on E12 resulted in a differential response to amphetamine in affected offspring, which may implicate a role for MIA in increasing the risk for disorders associated with this pathway, including drug tolerance and addiction.

Le cognitive enhancement en milieu universitaire : entre souffrance psychique individuelle, culture de performance et insécurités sociales

Ce projet de mémoire s’intéresse à la mise en relation du cognitive enhancement observé dans les universités occidentales contemporaines et de la société dans laquelle il s’insère. Nous avons voulu détacher la perspective du phénomène des analyses principalement orientées vers les programmes de sciences de la santé et de droit, ainsi que de l’approche quantitative, clinique, athéorique et somme toute moralisatrice qui lui est usuellement accordée afin d’explorer la nature des pratiques d’usages de psychotropes des étudiants universitaires en sciences humaines et sociales en vue d’augmenter leurs performances cognitives, d’approfondir la compréhension des raisonnements sous-jacents à ces pratiques, puis de resituer ces derniers dans leur contexte élargi. Nous avons interrogé treize étudiants de divers programmes de sciences humaines et sociales consommant, ou ayant déjà consommé, des psychotropes en vue de rehausser leurs performances cognitives en contexte académique. Les résultats suggèrent un écart dans la nature de leurs pratiques d’usage par rapport aux domaines d’études habituellement préconisés en ce sens qu’une grande variété de substances sont considérées comme supports cognitifs ; ensuite, que le recours aux psychotropes dans une visée de performance cognitive s’éloigne des logiques de la nécessité médicale et de la toxicomanie. En premier lieu, le cognitive enhancement est associé par plusieurs à une souffrance psychique liée à une perte de repères existentiels et les étudiants y ont recours dans une optique de compréhension de soi et de quête de repères dans un monde qu’ils ressentent comme instable. En second lieu, la consommation de psychotropes s’apparente davantage à un désir de satisfaire aux conditions incertaines et menaçantes des demandes externes de performance telles qu’ils les appréhendent qu’à un souci de soigner quelque condition médicale de la cognition. Nous pensons que le rapport au psychotrope qu’entretiennent les étudiants universitaires en sciences humaines et sociales s’insère en toute cohérence dans les discours et injonctions contemporaines de performance, en ce sens que leur souffrance psychique individuelle expose les limites de ce que la société attend d’eux.

Doing Research with Vulnerable Populations: The Case of Intravenous Drug Users

Article

Role of Dopamine D2 Receptors in the Consolidation of Amphetamine-Cue Memory in Conditioned Activity in Rats

The neurotransmitter dopamine (DA) plays an essential role in reward-related incentive learning, whereby neutral stimuli gain the ability to elicit approach and other responses. In an incentive learning paradigm called conditioned activity, animals receive a stimulant drug in a specific environment over the course of several days. When then placed in that environment drug-free, they generally display a conditioned hyperactive response. Modulating DA transmission at different time points during the paradigm has been shown to disrupt or enhance conditioning effects. For instance, blocking DA D2 receptors before sessions generally impedes the acquisition of conditioned activity. To date, no studies have examined the role of D2 receptors in the consolidation phase of conditioned activity; this phase occurs immediately after acquisition and involves the stabilization of memories for long-term storage. To investigate this possible role, I trained Wistar rats (N = 108) in the conditioned activity paradigm produced by amphetamine (2.0 mg/kg, intraperitoneally) to examine the effects of the D2 antagonist haloperidol (doses 0.10, 0.25, 0.50, 0.75, 1.0, & 2.0 mg/kg, intraperitoneally) administered 5 min after conditioning sessions. Two positive control groups received haloperidol 1 h before conditioning sessions (doses 1.0 mg/kg and 2.0 mg/kg). The results revealed that post-session haloperidol at all doses tested did not disrupt the consolidation of conditioned activity, while pre-session haloperidol at 2.0 mg/kg prevented acquisition, with the 1.0 mg/kg group trending toward a block. Additionally, post-session haloperidol did not diminish activity during conditioning days, unlike pre-session haloperidol. One possible reason for these findings is that the consolidation phase may have begun earlier than when haloperidol was administered, since the conditioned activity paradigm uses longer learning sessions than those generally used in consolidation studies. Future studies may test if conditioned activity can be achieved with shorter sessions; if so, haloperidol would then be re-tested at an earlier time point. D2 receptor second messenger systems may also be investigated in consolidation. Since drug-related incentive stimuli can evoke cravings in those with drug addiction, a better understanding of the mechanisms of incentive learning may lead to the development of solutions for these individuals.

Asumiendo las consecuencias negativas de la adicción al juego

La adicción al juego no sólo se caracteriza por la pérdida de control ante el juego, sino que esta conducta tiende a generar problemas en los diferentes ámbitos de la vida del ludópata. Por ello, este aspecto se recoge en el Manual diagnóstico y estadístico de los trastornos mentales-5 (DSM-V) como uno de los criterios para realizar su valoración diagnóstica. Objetivo: describir y analizar los diferentes elementos que conforman la compleja problemática aparejada a esta adicción y que pueden terminar en situaciones de exclusión social. Método: Se opta por una metodología cualitativa que se ajusta mejor a los intereses del estudio. Como técnica se ha seleccionado la historia de vida, instrumento de evaluación que permite conocer la verdadera magnitud del problema desde el punto de vista de los afectados. Resultados. De manera general, se ha descubierto que ser ludópata tiene muchos más consecuentes que el problema económico evidente. No debemos despreciar las implicaciones de esta conducta a otros niveles: familiar, laboral, legal y social, que pueden considerarse, a medio plazo, como factores mucho más execrables que el del mero gasto económico. Conclusión. Es fácil avistar que los graves problemas que acarrea la adicción al juego son capaces de desmembrar el proyecto vital del ludópata y el de su familia. Todo vale, aunque para ello tenga que jugarse su puesto de trabajo, su casa, su familia, sus amistades, su estatus social y su propia dignidad.

Women, Drug use and Imprisonment. Intersectional Approach

Research on women prisoners and drug use is scarce in our context and needs theoretical tools to understand their life paths. In this article, I introduce an intersectional perspective on the experiences of women in prison, with particular focus on drug use. To illustrate this, I draw on the life story of one of the women interviewed in prison, in order to explore the axes of inequality in the lives of women in prison. These are usually presented as accumulated and articulated in complex and diverse ways. The theoretical tool of intersectionality allows us to gain an understanding of the phenomenon of women prisoners who have used drugs. This includes both the structural constraints in which they were embedded and the decisions they made, considering the circumstances of disadvantage in which they were immersed. This is a perspective which has already been intuitively present since the dawn of feminist criminology in the English-speaking world and can now be developed further due to new contributions in this field of gender studies.

Risk Consumption: Children and Online Gaming. The Problem of “Responsible Gambling”

Online gambling is a popular activity among adolescents. However, there has been a notable increase in the number of young people who suffer or are on the verge of pathological gambling. We review the impact of online gambling on young people and discuss the desiderability of the concept of “gambling responsibly” in order to alert of their risks and effectively prevent access to minors. The main factors associated with pathological gambling are the age of start, the family environment, the infl uence of advertising, the consumption of stimulants, and the attitudes of the peer group. Both the government and the gaming industry itself should consider these factors and develop comprehensive plans that ensure a safe and controlled model game. In this context, advertising must take into account criteria of consumer protection knowing that even if they are not allowed, children can easily have access to online gambling. All agents involved, including public and social agents, must provide mechanisms for prevention and awareness of a problem that arouses little social consciousness and excessive carelessness.