Racial and ethnic differences in the association of social cohesion and social capital with HIV testing.

HIV testing rates vary by race and ethnicity. Whether social capital indicators are related to HIV testing and whether these associations differ by race or ethnicity is unknown. Multivariable analysis was used to examine whether social capital (collective engagement and civic and social participation), including social cohesion (trust in neighbors, neighbors willing to help, feelings of belongingness) were associated with testing for HIV in the past 12 months. Participants were white, Black or African American, and Hispanic/Latino adults ages 18 to 44 (N = 2823) from the general population, in Philadelphia, PA who participated in the Southeastern Pennsylvania Household Health Surveys 2010 and 2012. Overall HIV testing in this sample was 42%, and was higher among women, and Black compared to white people. Mean social capital scores were significantly highest among whites. Greater trust in neighbors was associated with lower odds of testing for HIV (adjusted Odds Ratio[aOR]:0.61, 95% CI = 0.49-0.74), and this relationship varied by race/ethnicity, with stronger inverse associations among Hispanic/Latino (aOR = 0.43, p < 0.001) and white adults (aOR = 0.50, p < -0.001) than among Black adults (aOR = 0.75, p < 0.05). Greater neighborhood belongingness (aOR = 1.31, 95% CI = 1.11-1.54) and working together to improve the neighborhood (aOR = 1.33, 95%CI = 1.03-1.73) were associated with higher odds of testing for HIV. Different indicators of social capital were associated with higher as well as lower odds of testing for HIV. These patterns did not vary statistically by race or ethnicity. HIV testing prevention interventions will need to address social capital in design and implementation strategies.

Substrate-selective COX-2 inhibition as a novel strategy for therapeutic endocannabinoid augmentation.

Pharmacologic augmentation of endogenous cannabinoid (eCB) signaling is an emerging therapeutic approach for the treatment of a broad range of pathophysiological conditions. Thus far, pharmacological approaches have focused on inhibition of the canonical eCB inactivation pathways - fatty acid amide hydrolase (FAAH) for anandamide and monoacylglycerol lipase (MAGL) for 2-arachidonoylglycerol. We review here the experimental evidence that cyclooxygenase-2 (COX-2)-mediated eCB oxygenation represents a third mechanism for terminating eCB action at cannabinoid receptors. We describe the development, molecular mechanisms, and in vivo validation of 'substrate-selective' COX-2 inhibitors (SSCIs) that prevent eCB inactivation by COX-2 without affecting prostaglandin (PG) generation from arachidonic acid (AA). Lastly, we review recent data on the potential therapeutic applications of SSCIs with a focus on neuropsychiatric disorders.

Multiple mechanistically distinct modes of endocannabinoid mobilization at central amygdala glutamatergic synapses.

The central amygdala (CeA) is a key structure at the limbic-motor interface regulating stress responses and emotional learning. Endocannabinoid (eCB) signaling is heavily implicated in the regulation of stress-response physiology and emotional learning processes; however, the role of eCBs in the modulation of synaptic efficacy in the CeA is not well understood. Here we describe the subcellular localization of CB1 cannabinoid receptors and eCB synthetic machinery at glutamatergic synapses in the CeA and find that CeA neurons exhibit multiple mechanistically and temporally distinct modes of postsynaptic eCB mobilization. These data identify a prominent role for eCBs in the modulation of excitatory drive to CeA neurons and provide insight into the mechanisms by which eCB signaling and exogenous cannabinoids could regulate stress responses and emotional learning.

Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice.

RATIONALE: Central CB1 cannabinoid receptors regulate anxiety-like and appetitive consummatory behaviors. Pharmacological antagonism/inverse-agonism of CB1 receptors increases anxiety and decreases appetitive behaviors; however, neither well-defined dose nor context dependence of these effects has been simultaneously assessed in one behavioral assay. OBJECTIVES: We sought to determine the context and dose dependence of the effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in a model that allowed for simultaneous detection of anxiety-like and consummatory-related behaviors. METHODS: We determined the effects of the CB1 receptor antagonist/inverse-agonist, rimonabant, in the novelty-induced hypophagia (NIH) assay in juvenile male ICR mice. RESULTS: Rimonabant dose-dependently decreased consumption of a palatable reward solution completely independent of contextual novelty. Grooming and scratching behavior was also increased by rimonabant in a context-independent manner. In contrast, rimonabant increased feeding latency, a measure of anxiety-like behaviors, only in a novel, mildly anxiogenic context. The effects of rimonabant were specific since no effects of rimonabant on despair-like behavior were observed in the tail suspension assay. Blockade of CB2 receptors had no effect on novelty-induced increases in feeding latency or palatable food consumption. CONCLUSIONS: Our findings indicate that CB1 receptor blockade decreases the hedonic value of palatable food irrespective of environmental novelty, whereas the anxiogenic-like effects are highly context-dependent. Blockade of CB2 receptors does not regulate either anxiety-like or consummatory behaviors in the NIH assay. These findings suggest that rimonabant modulates distinct and dissociable neural processes regulating anxiety and consummatory behavior to sculpt complex and context-dependent behavioral repertories.