Role of dorsomedial striatum neuronal ensembles in incubation of methamphetamine craving after voluntary abstinence

Abstract We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to self-administer palatable food pellets (6 d, 6 h/d) and methamphetamine (12 d, 6 h/d). We then assessed relapse to methamphetamine seeking under extinction conditions after 1 and 21 abstinence days. Between tests, the rats underwent voluntary abstinence (using a discrete choice procedure between methamphetamine and food; 20 trials/d) for 19 d. We used in situ hybridization to measure the colabeling of the activity marker Fos with Drd1 and Drd2 in DMS and DLS after the tests. Based on the in situ hybridization colabeling results, we tested the causal role of DMS D1 and D2 family receptors, and DMS neuronal ensembles in "incubated" methamphetamine seeking, using selective dopamine receptor antagonists (SCH39166 or raclopride) and the Daun02 chemogenetic inactivation procedure, respectively. Methamphetamine seeking was higher after 21 d of voluntary abstinence than after 1 d (incubation of methamphetamine craving). The incubated response was associated with increased Fos expression in DMS but not in DLS; Fos was colabeled with both Drd1 and Drd2 DMS injections of SCH39166 or raclopride selectively decreased methamphetamine seeking after 21 abstinence days. In Fos-lacZ transgenic rats, selective inactivation of relapse test-activated Fos neurons in DMS on abstinence day 18 decreased incubated methamphetamine seeking on day 21. Results demonstrate a role of DMS dopamine D1 and D2 receptors in the incubation of methamphetamine craving after voluntary abstinence and that DMS neuronal ensembles mediate this incubation. SIGNIFICANCE STATEMENT: In human addicts, abstinence is often self-imposed and relapse can be triggered by exposure to drug-associated cues that induce drug craving. We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we used classical pharmacology, in situ hybridization, immunohistochemistry, and the Daun02 inactivation procedure to demonstrate a critical role of dorsomedial striatum neuronal ensembles in this new form of incubation of drug craving

Tracking Lysosome Migration within Chinese Hamster Ovary (CHO) Cells Following Exposure to Nanosecond Pulsed Electric Fields

Above a threshold electric field strength, 600 ns-duration pulsed electric field (nsPEF) exposure substantially porates and permeabilizes cellular plasma membranes in aqueous solution to many small ions. Repetitive exposures increase permeabilization to calcium ions (Ca2+) in a dosage-dependent manner. Such exposure conditions can create relatively long-lived pores that reseal after passive lateral diffusion of lipids should have closed the pores. One explanation for eventual pore resealing is active membrane repair, and an ubiquitous repair mechanism in mammalian cells is lysosome exocytosis. A previous study shows that intracellular lysosome movement halts upon a 16.2 kV/cm, 600-ns PEF exposure of a single train of 20 pulses at 5 Hz. In that study, lysosome stagnation qualitatively correlates with the presence of Ca2+ in the extracellular solution and with microtubule collapse. The present study tests the hypothesis that limitation of nsPEF-induced Ca2+ influx and colloid osmotic cell swelling permits unabated lysosome translocation in exposed cells. The results indicate that the efforts used herein to preclude Ca2+ influx and colloid osmotic swelling following nsPEF exposure did not prevent attenuation of lysosome translocation. Intracellular lysosome movement is inhibited by nsPEF exposure(s) in the presence of PEG 300-containing solution or by 20 pulses of nsPEF in the presence of extracellular calcium. The only cases with no significant decreases in lysosome movement are the sham and exposure to a single nsPEF in Ca2+-free solution

Erratum : Squeezing and entanglement delay using slow light

An inconsistency was found in the equations used to calculate the variance of the quadrature fluctuations of a field propagating through a medium demonstrating electromagnetically induced transparency (EIT). The decoherence term used in our original paper introduces inconsistency under weak probe approximation. In this erratum we give the Bloch equations with the correct dephasing terms. The conclusions of the original paper remain the same. Both entanglement and squeezing can be delayed and preserved using EIT without adding noise when the decoherence rate is small.Comment: 1 page, no figur

Paired atom laser beams created via four-wave mixing

A method to create paired atom laser beams from a metastable helium atom laser via four-wave mixing is demonstrated. Radio frequency outcoupling is used to extract atoms from a Bose Einstein condensate near the center of the condensate and initiate scattering between trapped and untrapped atoms. The unequal strengths of the interactions for different internal states allows an energy-momentum resonance which leads to the creation of pairs of atoms scattered from the zero-velocity condensate. The resulting scattered beams are well separated from the main atom laser in the 2-dimensional transverse atom laser profile. Numerical simulations of the system are in good agreement with the observed atom laser spatial profiles, and indicate that the scattered beams are generated by a four-wave mixing process, suggesting that the beams are correlated.Comment: 5 pages, 3 figure

Optimal MRI sequences for 68Ga-PSMA-11 PET/MRI in evaluation of biochemically recurrent prostate cancer.

BackgroundPET/MRI can be used for the detection of disease in biochemical recurrence (BCR) patients imaged with 68Ga-PSMA-11 PET. This study was designed to determine the optimal MRI sequences to localize positive findings on 68Ga-PSMA-11 PET of patients with BCR after definitive therapy. Fifty-five consecutive prostate cancer patients with BCR imaged with 68Ga-PSMA-11 3.0T PET/MRI were retrospectively analyzed. Mean PSA was 7.9 ± 12.9 ng/ml, and mean PSA doubling time was 7.1 ± 6.6 months. Detection rates of anatomic correlates for prostate-specific membrane antigen (PSMA)-positive foci were evaluated on small field of view (FOV) T2, T1 post-contrast, and diffusion-weighted images. For prostate bed recurrences, the detection rate of dynamic contrast-enhanced (DCE) imaging for PSMA-positive foci was evaluated. Finally, the detection sensitivity for PSMA-avid foci on 3- and 8-min PET acquisitions was compared.ResultsPSMA-positive foci were detected in 89.1% (49/55) of patients evaluated. Small FOV T2 performed best for lymph nodes and detected correlates for all PSMA-avid lymph nodes. DCE imaging performed the best for suspected prostate bed recurrence, detecting correlates for 87.5% (14/16) of PSMA-positive prostate bed foci. The 8-min PET acquisition performed better than the 3-min acquisition for lymph nodes smaller than 1 cm, detecting 100% (57/57) of lymph nodes less than 1 cm, compared to 78.9% (45/57) for the 3-min acquisition.ConclusionPSMA PET/MRI performed well for the detection of sites of suspected recurrent disease in patients with BCR. Of the MRI sequences obtained for localization, small FOV T2 images detected the greatest proportion of PSMA-positive abdominopelvic lymph nodes and DCE imaging detected the greatest proportion of PSMA-positive prostate bed foci. The 8-min PET acquisition was superior to the 3 min acquisition for detection of small lymph nodes

High prevalence of scrapie in a dairy goat herd: tissue distribution of disease-associated PrP and effect of PRNP genotype and age

Following a severe outbreak of clinical scrapie in 2006–2007, a large dairy goat herd was culled and 200 animals were selected for post-mortem examinations in order to ascertain the prevalence of infection, the effect of age, breed and PRNP genotype on the susceptibility to scrapie, the tissue distribution of diseaseassociated PrP (PrP$^{\rm d}$), and the comparative efficiency of different diagnostic methods. As determined by immunohistochemical (IHC) examinations with Bar224 PrP antibody, the prevalence of preclinical infection was very high (72/200; 36.0%), with most infected animals being positive for PrP$^{\rm d}$ in lymphoreticular system (LRS) tissues (68/72; 94.4%) compared to those that were positive in brain samples (38/72; 52.8%). The retropharyngeal lymph node and the palatine tonsil showed the highest frequency of PrP$^{\rm d}$ accumulation (87.3% and 84.5%, respectively), while the recto-anal mucosa-associated lymphoid tissue (RAMALT) was positive in only 30 (41.7%) of the infected goats. However, the efficiency of rectal and palatine tonsil biopsies taken shortly before necropsy was similar. The probability of brain and RAMALT being positive directly correlated with the spread of PrP$^{\rm d}$ within the LRS. The prevalence of infection was influenced by PRNP genetics at codon 142 and by the age of the goats: methionine carriers older than 60 months showed a much lower prevalence of infection (12/78; 15.4%) than those younger than 60 months (20/42; 47.6%); these last showed prevalence values similar to isoleucine homozygotes of any age (40/80; 50.0%). Two of seven goats with definite signs of scrapie were negative for PrP$^{\rm d}$ in brain but positive in LRS tissues, and one goat showed biochemical and IHC features of PrP$^{\rm d}$ different from all other infected goats. The results of this study have implications for surveillance and control policies for scrapie in goats

Can optical squeezing be generated via polarization self-rotation in a thermal vapour cell?

The traversal of an elliptically polarized optical field through a thermal vapour cell can give rise to a rotation of its polarization axis. This process, known as polarization self-rotation (PSR), has been suggested as a mechanism for producing squeezed light at atomic transition wavelengths. In this paper, we show results of the characterization of PSR in isotopically enhanced Rubidium-87 cells, performed in two independent laboratories. We observed that, contrary to earlier work, the presence of atomic noise in the thermal vapour overwhelms the observation of squeezing. We present a theory that contains atomic noise terms and show that a null result in squeezing is consistent with this theory.Comment: 10 pages, 11 figures, submitted to PRA. Please email author for a PDF file if the article does not appear properl

HIV Epidemics in the European Region: Vulnerability and Response

This report provides a systematic review of the evidence on HIV vulnerability and response in all 53 countries of the WHO European Region, stretching from Iceland to the borders of China. It focuses on key populations most at risk of HIV infection: people who inject drugs, sex workers and men who have sex with men. It confirms that these populations are disproportionately affected by the growing HIV epidemic in Europe. Twenty-five percent of HIV diagnoses in Europe are associated with injecting drug use, with much higher proportions in Eastern Europe (33%) than in Western Europe (5%) and Central Europe (7%). Sex between men accounted for 10% of all HIV diagnoses, with higher rates reported in Western Europe (36%), followed by Central Europe (22%) and Eastern Europe (0.5%). HIV remains relatively low among female sex workers who do not inject drugs, (less than 1%), but higher among those who inject drugs (over 10%) as well as among male and transgender sex workers. The analysis highlights the pivotal role of social and structural factors in shaping HIV epidemics and HIV prevention responses. Poverty, marginalization and stigma contribute to the HIV epidemic in Europe and Central Asia. Economic volatility and recession risks are increasing vulnerability to HIV and infections. Barriers to successful HIV responses include the criminalization of sex work, of sex between men, and of drug use combined with social stigmatization, violence and rights violations. HIV prevention requires social and environmental change. The report calls for policymakers and HIV program implementers to target the right policies and programs to maximize the health and social impacts of Europe’s HIV responses and get higher returns on HIV-related investments. The report is a product of a collaboration between the World Bank, the London School of Hygiene and Tropical Medicine, the WHO Regional Office for Europe and UNAIDS

Evolución del diseño de interiores en los grandes Centros Comerciales de Lima Central Sur en las últimas tres décadas

La investigación responde a una problemática que se evidencia a través de una serie de debilidades que repercuten en el diseño de dichos centros comerciales. El conocimiento de nuevas tecnologías para el diseño interior era escaso, no había conocimientos de enchapes, acabados finos, iluminación decorativa y diseño interior en general. Los materiales tampoco eran de gran ayuda, solo se conocían las estructuras comunes, como el cemento y el acero. Tampoco había conocimientos sobre técnicas constructivas