Cocaine Serves as a Peripheral Interoceptive Conditioned Stimulus for Central Glutamate and Dopamine Release

Intravenous injections of cocaine HCl are habit-forming because, among their many actions, they elevate extracellular dopamine levels in the terminal fields of the mesocorticolimbic dopamine system. This action, thought to be very important for cocaine's strong addiction liability, is believed to have very short latency and is assumed to reflect rapid brain entry and pharmacokinetics of the drug. However, while intravenous cocaine HCl has almost immediate effects on behavior and extracellular dopamine levels, recent evidence suggests that its central pharmacological effects are not evident until 10 or more seconds after IV injection. Thus the immediate effects of a given intravenous cocaine injection on extracellular dopamine concentration and behavior appear to occur before there is sufficient time for cocaine to act centrally as a dopamine uptake inhibitor. To explore the contribution of peripheral effects of cocaine to the early activation of the dopamine system, we used brain microdialysis to measure the effects of cocaine methiodide (MI)—a cocaine analogue that does not cross the blood brain barrier—on glutamate (excitatory) input to the dopamine cells. IP injections of cocaine MI were ineffective in cocaine-naïve animals but stimulated ventral tegmental glutamate release in rats previously trained to lever-press for cocaine HCl. This peripherally triggered glutamate input was sufficient to reinstate cocaine-seeking in previously trained animals that had undergone extinction of the habit. These findings offer an explanation for short-latency behavioral responses and immediate dopamine elevations seen following cocaine injections in cocaine-experienced but not cocaine-naïve animals

Reduced prefrontal gyrification in obsessive–compulsive disorder

Structural magnetic resonance imaging (MRI) studies reveal evidence for brain abnormalities in obsessive–compulsive disorder (OCD), for instance, reduction of gray matter volume in the prefrontal cortex. Disturbances of gyrification in the prefrontal cortex have been described several times in schizophrenia pointing to a neurodevelopmental etiology, while gyrification has not been studied so far in OCD patients. In 26 OCD patients and 38 healthy control subjects MR-imaging was performed. Prefrontal cortical folding (gyrification) was measured bilaterally by an automated version of the automated-gyrification index (A-GI), a ratio reflecting the extent of folding, from the slice containing the inner genu of the corpus callosum up to the frontal pole. Analysis of covariance (ANCOVA, independent factor diagnosis, covariates age, duration of education) demonstrated that compared with control subjects, patients with OCD displayed a significantly reduced A-GI in the left hemisphere (p = 0.021) and a trend for a decreased A-GI in the right hemisphere (p = 0.076). Significant correlations between prefrontal lobe volume and A-GI were only observed in controls, but not in OCD patients. In conclusion, prefrontal hypogyrification in OCD patients may be a structural correlate of the impairment in executive function of this patient group and may point to a neurodevelopmental origin of this disease

The volcanic history of Pyrgousa—volcanism before the eruption of the Kos Plateau Tuff

The islet of Pyrgousa, 8 km west of Nisyros, has andesites overlain by proximal deposits of the Kos Plateau Tuff (KPT). These andesites record the evolution of the Kos-Nisyros volcanic centre prior to the large KPT eruption at 161 ka. This precursory activity had previously been recorded only in dacites and rhyolites in the Kefalos Peninsula, farther from the volcanic centre. This study investigated the age, geochemistry, mineralogy, and petrogenesis of the andesite domes, probable flows, and associated talus breccias on Pyrgousa. Analysed samples are basaltic andesite and andesite, with strong enrichment in Ba and Sr and low values of Ti and Zr. An 40Ar/39Ar date of 1.9 ± 0.1 Ma on biotite is similar to dates from dacite and rhyolite stocks and domes in the Kefalos Peninsula, and like those dates is the maximum age due to excess 40Ar. There is no evidence on Pyrgousa for a stratovolcano precursor of the KPT eruption. The andesite domes geochemically resemble Pliocene domes in Methana and Aegina that mark the onset of magmatism in the northwestern South Aegean Arc, with an important magma component derived from subcontinental lithospheric mantle. These early andesites heated the upper crust, thus facilitating the growth of upper crustal magma chambers, which were filled by felsic crystal mush derived by differentiation of hydrous intermediate magmas with a more asthenospheric signature. © 2019, Crown

Interferon-γ Induces Expression of MHC Class II on Intestinal Epithelial Cells and Protects Mice from Colitis

Immune responses against intestinal microbiota contribute to the pathogenesis of inflammatory bowel diseases (IBD) and involve CD4(+) T cells, which are activated by major histocompatibility complex class II (MHCII) molecules on antigen-presenting cells (APCs). However, it is largely unexplored how inflammation-induced MHCII expression by intestinal epithelial cells (IEC) affects CD4(+) T cell-mediated immunity or tolerance induction in vivo. Here, we investigated how epithelial MHCII expression is induced and how a deficiency in inducible epithelial MHCII expression alters susceptibility to colitis and the outcome of colon-specific immune responses. Colitis was induced in mice that lacked inducible expression of MHCII molecules on all nonhematopoietic cells, or specifically on IECs, by continuous infection with Helicobacter hepaticus and administration of interleukin (IL)-10 receptor-blocking antibodies (anti-IL10R mAb). To assess the role of interferon (IFN)-γ in inducing epithelial MHCII expression, the T cell adoptive transfer model of colitis was used. Abrogation of MHCII expression by nonhematopoietic cells or IECs induces colitis associated with increased colonic frequencies of innate immune cells and expression of proinflammatory cytokines. CD4(+) T-helper type (Th)1 cells - but not group 3 innate lymphoid cells (ILCs) or Th17 cells - are elevated, resulting in an unfavourably altered ratio between CD4(+) T cells and forkhead box P3 (FoxP3)(+) regulatory T (Treg) cells. IFN-γ produced mainly by CD4(+) T cells is required to upregulate MHCII expression by IECs. These results suggest that, in addition to its proinflammatory roles, IFN-γ exerts a critical anti-inflammatory function in the intestine which protects against colitis by inducing MHCII expression on IECs. This may explain the failure of anti-IFN-γ treatment to induce remission in IBD patients, despite the association of elevated IFN-γ and IBD

Gambling careers: a longitudinal, qualitative study of gambling behaviour

This article presents findings from a five year study of ‘gambling careers’ designed to explore the ways that individuals move in and out of problematic behaviour over time. A longitudinal qualitative methodology was used to investigate patterns of stability and change in a cohort of 50 problem and recreational gamblers. The study found that change, rather than stability, was the norm in gambling behaviour and identified four different trajectories of behaviour: progression, reduction, consistency and non-linearity. Drawing on rich narrative accounts of respondents’ gambling behaviour, the study begins to suggest reasons for these different types of movement, highlighting the role of material factors such as employment, environment and social context in each. It concludes that gambling behaviour is highly variable over time, and recommends that future research focus on patterns of behaviour rather than on ‘types’ of gamblers