Cannabinoid Modulation of Reinforcement Maintained by Stimulation of the Medial Forebrain Bundle in C57Bl/6J Mice

Cannabinoid agonists, including marijuana containing delta-9-tetrahydrocannabinol (THC), are found rewarding by humans. In addition to human self-reports and experimental studies that show marijuana is rewarding, contributions from preclinical studies also have implicated cannabinoid receptors in reward-motivated behavior. One way to assess these preclinical effects of cannabinoids is intracranial self-stimulation (ICSS), where an animal performs a response to receive electrical stimulation of a specific brain area or circuit known to be involved in reward. Drugs of abuse, such as psychomotor stimulants, facilitate responding for ICSS. While a few studies have shown facilitating effects of cannabinoids in rats, several have shown the opposite effect, and no studies so far have evaluated cannabinoids in mouse ICSS. Furthermore there are no studies evaluating specific inhibitors of endocannabinoid catabolic enzymes in ICSS in any species. In these studies we assessed the cannabinoid agonist THC, as well as the fatty acid amide hydrolase (FAAH) inhibitor, PF-3845, the monoacylglycerol lipase (MAGL) inhibitor JZL184, and the combined FAAH/MAGL inhibitor SA-57 in ICSS of the medial forebrain bundle in C57BL/6 mice. Additionally, we assessed the psychomotor stimulant cocaine as a positive control to facilitate ICSS. These studies were complimented with spontaneous locomotor activity and food-maintained operant experiments to assess the sensitivity of ICSS to cannabinoids. Additionally, brain endocannabinoid levels were measured in brain regions associated with the mesolimbic system after enzyme inhibitor treatments. THC, JZL184, and SA-57 all produced time-dependent reductions in ICSS that were mediated through CB1 receptors, as they were blocked by pre-treatment with the CB1 antagonist rimonabant, but not with the CB2 antagonist SR144528. PF-3845 also reduced ICSS, but did so independent of CB1 and CB2 receptors, and only with one dose (30.0 mg/kg) that has not been assessed previously in vivo. We showed that ICSS was more sensitive to the rate-reducing effects of cannabinoids than other measures of behavior with motor components including spontaneous locomotor activity and operant nose-poking for food, and that the reduction of ICSS produced by both JZL184 and SA-57 is accompanied by increases in 2-AG in mesolimbic brain areas. Thus, cannabinoids do not facilitate ICSS in C57BL/6 mice over a range of doses and pre-treatment times, similar to most studies with rats. These data suggest that cannabinoids may produce rewarding effects through non-mesolimbic areas of the brain

Syrian diaspora mobilization for prospective transitional justice in the absence of transition

Mobilization for transitional justice typically “deals with the past,” focusing on retrospective attempts to deal with injustices. Little attention has been afforded to such mobilization when prospects for transition and justice are remote. The Syrian diaspora persistently mobilizes for what we call prospective transitional justice despite unfavorable circumstances. This article asks why. First, they have a sense of moral obligation to do so. Second, framing claims in terms of transitional justice and human rights is perceived as the best strategy to transform Syrian society. Third, transitional justice discourse is an avenue through which diaspora organizations secure institutional survival.publishedVersio

The evolution of funding for the International Criminal Court: budgets, donors and gender justice

In this article, we introduce a new dataset on financial support for the International Criminal Court (ICC) and examine how this support has changed over its two decades of existence. We first consider how the ICC’s overall budget has changed over time. Then, we explore the evolution of support from individual donor governments. In addition, given former Prosecutor Bensouda’s emphasis on the effective investigation and prosecution of sexual and gender-based crimes, we examine the extent to which ICC funding is consistent with its apparent commitment to gender justice. Our research contributes to debates about the cost of justice, donors and norm diffusion, South–North clashes over the definition and delivery of justice, and gender mainstreaming within costly international justice processes. We argue that the level of funding state parties and other bodies allocate to particular forms of justice is a better proxy for their commitment to justice than their rhetoric, and conclude that the patterns of funding seen at the ICC support the claim that the Court remains, to a significant extent, a tool of powerful states

Effects of Classroom-Based Physical Activities on Off-Task Behaviors and Attention: Kindergarten Case Study

The qualitative case study’s purpose was to determine if classroom-based physical activities would affect student off-task behaviors during instruction and students’ perceptions of ability to focus before and after activities. Research questions focused on kindergarteners’ ability to focus after classroom-based physical activity, perceptions of their ability to focus change with implementation of classroom-based physical activity, and effect of classroom-based physical activity on behavior. Kindergarteners were involved in daily activity stations such as jumping on trampolines, walking balance beams, crawling, and hopscotch. Three students were purposively selected as participants. Data were collected using interviews, video recordings, field notes, and off-task behavior frequency charts and analyzed using a constant comparative method. Study results indicated that implementation of classroom-based physical activities decreased students’ off-task behaviors. Decrease in off-task behaviors increased students’ perceptions of their ability to pay attention and remain on-task. Recommendations for future research include using a control group and participants diagnosed with ADHD

The Quantitative Turn in Transitional Justice Research: What Have We Learned About Impact?

In recent years, scholars have increasingly turned to quantitative research methods to understand the impact of transitional justice (TJ) on societies emerging from periods of violence and repression. This research often seeks to influence policy diffusion by making bold claims based upon large datasets of TJ events that span space and time. However, the policy advice from the first wave of quantitative research is inconsistent if not contradictory. In this article, we outline a range of methodological issues that help to explain the different conclusions reached by these studies, including sampling strategies, model construction, and the measurement of key variables. Furthermore, these studies have often failed to provide compelling theoretical or empirical bases for a causal relationship between TJ mechanisms and dependent variables such as democracy and human rights. We suggest several ways in which quantitative scholars could produce findings with broader credibility. Although we support the use of quantitative methods to understand the impact of TJ mechanisms, greater methodological care is needed in supporting policy recommendations

EXAMINATION OF THE DISCRIMINATIVE STIMULUS AND CROSS-TOLERANCE INDUCING PROPERTIES OF N-DESMETHYLCLOZAPINE IN C57BL/6 MICE.

Due to its unique receptor binding profile and its relationship to clozapine, N-desmethylclozapine (NDMC) has been examined as a possible antipsychotic drug (APD). Clozapine has been trained as discriminative stimulus in our lab, but NDMC has not yet been established as a discriminative stimulus. In experiment 1, 12 C57BL/6 mice were trained to discriminate 10.0 mg/kg NDMC from VEH using a standard-two lever operant procedure to assess antipsychotic substitution. The typical APD clozapine fully substituted for NDMC at 2 doses tested (2.5 and 5.0 mg/kg), while typical APD haloperidol failed to substitute for NDMC. In Experiment 2, 11 mice were given repeated administration of NDMC to assess cross-tolerance development to the discriminative stimulus of clozapine. NDMC was successfully trained as a discriminative stimulus and was also shown to induce cross-tolerance to clozapine’s discriminative stimulus, indicating similar underlying pharmacological mechanisms of action between NDMC and clozapine