Corticotropin Releasing Factor Type 1 and 2 Receptor Signaling in the Medial Prefrontal Cortex Modulates Binge-Like Ethanol Consumption in C57BL/6J Mice

Corticotropin releasing factor (CRF) signaling via limbic CRF1 and 2 receptors (CRF1R and CRF2R, respectively) is known to modulate binge-like ethanol consumption in rodents. Though CRF signaling in the medial prefrontal cortex (mPFC) has been shown to modulate anxiety-like behavior and ethanol seeking, its role in binge ethanol intake is unknown. Here, we used "drinking-in-the-dark" (DID) procedures in male and female C57BL/6J mice to address this gap in the literature. First, the role of CRF1R and CRF2R signaling in the mPFC on ethanol consumption was evaluated through site-directed pharmacology. Next, we evaluated if CRF1R antagonist reduction of binge-intake was modulated in part through CRF2R activation by co-administration of a CRF1R and CRF2R antagonist. Intra-mPFC inhibition of CRF1R and activation of CRF2R resulted in decreased binge-like ethanol intake. Further, the inhibitory effect of the CRF1R antagonist was attenuated by co-administration of a CRF2R antagonist. We provide novel evidence that (1) inhibition of CRF1R or activation of CRF2R in the mPFC reduces binge-like ethanol intake; and (2) the effect of CRF1R antagonism may be mediated via enhanced CRF2R activation. These observations provide the first direct behavioral pharmacological evidence that CRF receptor activity in the mPFC modulates binge-like ethanol consumption

Parent perceptions and decision making about treatments for epilepsy : a qualitative evidence synthesis

Peer reviewedPublisher PD

Chemogenetic Inhibition of Corticotropin-Releasing Factor Neurons in the Central Amygdala Alters Binge-Like Ethanol Consumption in Male Mice

Repetitive bouts of binge drinking can lead to neuroplastic events that alter ethanol's pharmacologic effects and perpetuate excessive consumption. The corticotropin-releasing factor (CRF) system is an example of ethanol-induced neuroadaptations that drive excessive ethanol consumption. Our laboratory has previously shown that CRF antagonist, when infused into the central amygdala (CeA), reduces binge-like ethanol consumption. The present study extends this research by assessing the effects of silencing CRF-producing neurons in CeA on binge-like ethanol drinking stemming from "Drinking in the Dark" (DID) procedures. CRF-ires-Cre mice underwent surgery to infuse Gi/o-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus or a control virus into either the CeA or basolateral amygdala (BLA). Gi/o-DREADD-induced CRF-neuronal inhibition in the CeA resulted in a 33% decrease in binge-like ethanol consumption. However, no effect on ethanol consumption was seen after DREADD manipulation in the BLA. Moreover, CeA CRF-neuronal inhibition had no effect on sucrose consumption. The effects of silencing CRF neurons in the CeA on ethanol consumption are not secondary to changes in motor function or anxiety-like behaviors as assessed in the open-field test (OFT). Finally, the DREADD construct's functional ability to inhibit CRF-neuronal activity was demonstrated by reduced ethanol-induced c-Fos following DREADD activation. Together, these data suggest that the CRF neurons in the CeA play an important role in binge ethanol consumption and that inhibition of the CRF-signaling pathway remains a viable target for manipulating binge-like ethanol consumption

Morphological studies of the Spitzer Wide-Area Infrared Extragalactic survey galaxy population in the UGC 10214 Hubble space telescope/advanced camera for surveys field

We present the results of a morphological analysis of a small subset of the Spitzer Wide-Area Infrared Extragalactic survey (SWIRE) galaxy population. The analysis is based on public Advanced Camera for Surveys (ACS) data taken inside the SWIRE N1 field, which are the deepest optical high-resolution imaging available within the SWIRE fields as of today. Our reference sample includes 156 galaxies detected by both ACS and SWIRE. Among the various galaxy morphologies, we disentangle two main classes, spheroids (or bulge-dominated galaxies) and disc-dominated ones, for which we compute the number counts as a function of flux. We then limit our sample to objects with Infrared Array Camera (IRAC) fluxes brighter than 10 μJy, estimated ~90 per cent completeness limit of the SWIRE catalogues, and compare the observed counts to model predictions. We find that the observed counts of the spheroidal population agree with the expectations of a hierarchical model while a monolithic scenario predicts steeper counts. Both scenarios, however, underpredict the number of late-type galaxies. These observations show that the large majority (close to 80 per cent) of the 3.6- and 4.5-μm galaxy population, even at these moderately faint fluxes, is dominated by spiral and irregular galaxies or mergers

Medial prefrontal cortex neuropeptide Y modulates binge-like ethanol consumption in C57BL/6J mice

Neuropeptide Y (NPY) signaling via limbic NPY1 and 2 receptors (NPY1R and NPY2R, respectively) is known to modulate binge-like ethanol consumption in rodents. However, the role of NPY signaling in the medial prefrontal cortex (mPFC), which provides top-down modulation of the limbic system, is unknown. Here, we used “drinking-in-the-dark” (DID) procedures in C57BL/6J mice to address this gap in the literature. First, the impact of DID on NPY immunoreactivity (IR) was assessed in the mPFC. Next, the role of NPY1R and NPY2R signaling in the mPFC on ethanol consumption was evaluated through site-directed pharmacology. Chemogenetic inhibition of NPY1R+ neurons in the mPFC was performed to further evaluate the role of this population. To determine the potential role of NPY1R+ neurons projecting from the mPFC to the basolateral amygdala (BLA) this efferent population was selectively silenced. Three, 4-day cycles of DID reduced NPY IR in the mPFC. Intra-mPFC activation of NPY1R and antagonism of NPY2R resulted in decreased binge-like ethanol intake. Silencing of mPFC NPY1R+ neurons overall, and specifically NPY1R+ neurons projecting to the BLA, significantly reduced binge-like ethanol intake. We provide novel evidence that (1) bingelike ethanol intake reduces NPY levels in the mPFC; (2) activation of NPY1R or blockade of NPY2R reduces binge-like ethanol intake; and (3) chemogenetic inhibition of NPY1R+ neurons in the mPFC and NPY1R+ mPFC neurons projecting to the BLA blunts bingelike drinking

Distinct and Overlapping Patterns of Acute Ethanol-Induced C-Fos Activation in Two Inbred Replicate Lines of Mice Selected for Drinking to High Blood Ethanol Concentrations

The inbred high drinking in the dark (iHDID1 and iHDID2) strains are two replicate lines bred from the parent HS/Npt (HS) line for achieving binge levels of blood ethanol concentration (≥80 mg/dL BEC) in a four-hour period. In this work, we sought to evaluate differences in baseline and ethanol-induced c-Fos activation between the HS, iHDID1, and iHDID2 genetic lines in brain regions known to process the aversive properties of ethanol. METHODS: Male and female HS, iHDID1, and iHDID2 mice underwent an IP saline 2 3 g/kg ethanol injection. Brain sections were then stained for c-Fos expression in the basolateral/central amygdala (BLA/CeA), bed nucleus of the stria terminals (BNST), A2, locus coeruleus (LC), parabrachial nucleus (PBN), lateral/medial habenula (LHb/MHb), paraventricular nucleus of the thalamus (PVT), periaqueductal gray (PAG), Edinger-Westphal nuclei (EW), and rostromedial tegmental nucleus (RMTg). RESULTS: The iHDID1 and iHDID2 lines showed similar and distinct patterns of regional c-Fos; however, in no region did the two both significantly differ from the HS line together. CONCLUSIONS: These data lend further support to altered baseline or ethanol-induced activation in brain regions associated with processing the aversive properties of ethanol in the iHDID1 and iHDID2 genetic lines

Remarkable Disk and Off-nuclear Starburst Activity in the "Tadpole Galaxy" as revealed by the Spitzer Space Telescope

We present ground-based optical and Spitzer infrared imaging observations of the interacting galaxy UGC 10214, the "Tadpole Galaxy" (z = 0.0310), focusing on the star formation activity in the nuclear, disk, spiral arms and tidal tail regions. The major findings of this study are that the Tadpole is actively forming stars in the main disk outside of the nucleus and in the tidal plume, with an estimated mean star formation rate of ~2 to 4 M_sun/yr. The most prominent sites of mid-infrared emission define a "ring" morphology that, combined with the overall morphology of the system, suggest the interaction may belong to the rare class of off-center collisional ring systems that form both shock-induced rings of star formation and tidal plumes. The nuclear emission is solely powered by older stars, with little evidence for ongoing star formation at the center of the Tadpole. Extra-nuclear star formation accounts for >50% of the total star formation in the disk and spiral arms, featuring infrared-bright 'hot spots' that exhibit strong PAH emission, whose band strength is comparable to that of late-type star-forming disk galaxies. The tidal tail, which extends 2 arcmin (~75 kpc) into the intergalactic medium, is populated by super massive star clusters likely triggered by the galaxy-galaxy interaction that has distorted UGC 10214 into its current "tadpole" shape.Comment: to appear in the January 2006 (vol 131) issue of the Astronomical Journal; high quality graphics are located here: http://spider.ipac.caltech.edu/staff/jarrett/tadpole.htm

Emission Features and Source Counts of Galaxies in Mid-Infrared

In this work we incorporate the newest ISO results on the mid-infrared spectral-energy-distributions (MIR SEDs) of galaxies into models for the number counts and redshift distributions of MIR surveys. A three-component model, with empirically determined MIR SED templates of (1) a cirrus/PDR component (2) a starburst component and (3) an AGN component, is developed for infrared (3--120\micron) SEDs of galaxies. The model includes a complete IRAS 25\micron selected sample of 1406 local galaxies ($z \leq 0.1$; Shupe et al. 1998a). Results based on these 1406 spectra show that the MIR emission features cause significant effects on the redshift dependence of the K-corrections for fluxes in the WIRE 25\micron band and ISOCAM 15\micron band. This in turn will affect deep counts and redshift distributions in these two bands, as shown by the predictions of two evolution models (a luminosity evolution model with $L\propto (1+z)^3$ and a density evolution model with $\rho\propto (1+z)^4$). The dips-and-bumps on curves of MIR number counts, caused by the emission features, should be useful indicators of evolution mode. The strong emission features at $\sim 6$--8\micron will help the detections of relatively high redshift ($z\sim 2$) galaxies in MIR surveys. On the other hand, determinations of the evolutionary rate based on the slope of source counts, and studies on the large scale structures using the redshift distribution of MIR sources, will have to treat the effects of the MIR emission features carefully. We have also estimated a 15\micron local luminosity function from the predicted 15\micron fluxes of the 1406 galaxies using the bivariate (15\micron vs. 25\micron luminosities) method. This luminosity function will improve our understanding of the ISOCAM 15\micron surveys.Comment: 24 pages, 14 EPS figures. Accepted by Ap

Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt