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San Fedele Superiore, Italy

Malkesman O.,National Health Research Institute | Scattoni M.L.,Instituto Superiore Of Sanita | Scattoni M.L.,National Institute of Mental Health | Paredes D.,U.S. National Institutes of Health | And 6 more authors.
Biological Psychiatry | Year: 2010

Background: Abnormal hedonic behavior is a key feature of many psychiatric disorders. Several paradigms measure reward-seeking behavior in rodents, but each has limitations. We describe a novel approach for monitoring reward-seeking behavior in rodents: sniffing of estrus female urine by male mice, along with number of ultrasonic vocalizations (USVs) emitted during the test. Methods: The female urine sniffing test (FUST) was designed to monitor reward-seeking activity in rodents together with tests of helplessness and sweet solution preference. USVs and dopamine release from the nucleus accumbens (NAc) were recorded. Sniffing activity was measured in 1) manipulation-naive C57BL/6J and 129S1/SVImJ mice and Wistar-Kyoto rats; 2) stressed mice; 3) two groups of mice that underwent the learned helplessness paradigm-one untreated, and one treated with the SSRI citalopram; and 4) GluR6 knockout mice, known to display lithium-responsive, mania-related behaviors. Results: Males from all three strains spent significantly longer sniffing female urine than sniffing water. Males emitted USVs and showed significantly elevated NAc dopamine levels while sniffing urine. Foot-shock stress significantly reduced female urine sniffing time. Compared with mice that did not undergo the LH paradigm, LH males spent less time sniffing female urine, and citalopram treatment alleviated this reduction. Compared with their wildtype littermates, GluR6KO males sniffed female urine longer and showed enhanced saccharin preference. Conclusions: In rodents, sniffing female urine is a preferred activity accompanied by biological changes previously linked to reward-seeking activities. The FUST is sensitive to behavioral and genetic manipulation and to relevant drug treatment. © 2010 Society of Biological Psychiatry.

Campolongo P.,University of Rome La Sapienza | Morena M.,University of Rome La Sapienza | Scaccianoce S.,University of Rome La Sapienza | Trezza V.,Third University of Rome | And 4 more authors.
Neuropsychopharmacology | Year: 2013

Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short-and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1-and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short-and long-term retention of object recognition memory. © 2013 American College of Neuropsychopharmacology.

Litzba N.,Robert Koch Institute | Zelena H.,Institute of Public Health | Kreil T.R.,Baxter Bioscience | Niklasson B.,Uppsala University | And 3 more authors.
Vector-Borne and Zoonotic Diseases | Year: 2014

Tick-borne encephalitis (TBE) is a zoonotic disease, transmitted mainly by the bite of ticks. The TBE virus (TBEV) belongs to the family Flaviviridae, genus Flavivirus and is able to cause meningoencephalitis. For serological TBEV detection, the neutralization test (NT) is the most specific assay available. Different NT protocols are used in the laboratories, and until now the performance of these NTs has never been tested in an external quality assessment (EQA). In this EQA, we compared the results of eight European laboratories in detecting 17 samples (11 TBEV positive, five flavivirus cross reactive, and one negative sample) by NT. Furthermore, 14 of these EQA samples and 15 additional samples were tested in different commercial assays: 15 immunoglobulin G (IgG) enzyme-linked immunosorbent assays (ELISAs) and an immunofluorescence assay (IFA). Four laboratories showed a good NT EQA performance, whereas four laboratories had some sensitivity problems. Additionally, two of these laboratories showed a lack in specificity, misidentifying a dengue-positive sample as TBEV positive. The comparison of the commercial ELISAs revealed a high sensitivity in all assays, but as expected for IgG, the ELISAs showed a high degree of flavivirus cross reactivity. The assessment of Vienna Units in some of the ELISAs revealed deviations in the standards used by the different companies. Therefore, these standards should be revised. Generally, in this EQA, we found that reliable NT protocols are used in most of the laboratories, and the evaluation of the IgG ELISAs and the IFA showed a good agreement. © 2014, Mary Ann Liebert, Inc. 2014.

Lyon L.,University of Oxford | Burnet P.W.J.,University of Oxford | Kew J.N.C.,Glaxosmithkline | Corti C.,Glaxosmithkline | And 5 more authors.
Neuropsychopharmacology | Year: 2011

Group II metabotropic glutamate receptors (mGluR2 and mGluR3, encoded by GRM2 and GRM3) are implicated in hippocampal function and cognition, and in the pathophysiology and treatment of schizophrenia and other psychiatric disorders. However, pharmacological and behavioral studies with group II mGluR agonists and antagonists have produced complex results. Here, we studied hippocampus-dependent memory in GRM2/3 double knockout (GRM2/3 -/-) mice in an iterative sequence of experiments. We found that they were impaired on appetitively motivated spatial reference and working memory tasks, and on a spatial novelty preference task that relies on animals exploratory drive, but were unimpaired on aversively motivated spatial memory paradigms. GRM2/3 -/- mice also performed normally on an appetitively motivated, non-spatial, visual discrimination task. These results likely reflect an interaction between GRM2/3 genotype and the arousal-inducing properties of the experimental paradigm. The deficit seen on appetitive and exploratory spatial memory tasks may be absent in aversive tasks because the latter induce higher levels of arousal, which rescue spatial learning. Consistent with an altered arousal-cognition relationship in GRM2/3 -/- mice, injection stress worsened appetitively motivated, spatial working memory in wild-types, but enhanced performance in GRM2/3 -/- mice. GRM2/3 -/- mice were also hypoactive in response to amphetamine. This fractionation of hippocampus-dependent memory depending on the appetitive-aversive context is to our knowledge unique, and suggests a role for group II mGluRs at the interface of arousal and cognition. These arousal-dependent effects may explain apparently conflicting data from previous studies, and have translational relevance for the involvement of these receptors in schizophrenia and other disorders. © 2011 American College of Neuropsychopharmacology. All rights reserved.

Weiss E.P.,University of Washington | Weiss E.P.,Washington University in St. Louis | Villareal D.T.,University of Washington | Villareal D.T.,University of New Mexico | And 4 more authors.
Aging | Year: 2011

Plasma dehydroepiandrosterone (DHEA) decreases ~80% between ages 25 and 75 yr. In a preliminary study, we found that 6 mo of DHEA replacement improved insulin action in elderly individuals. The purpose of the present larger, randomized double-blind study was to determine whether a longer period of DHEA replacement improves glucose tolerance. Fifty-seven men and 68 women aged 65 to 75 yr were randomly assigned to 50 mg DHEA or placebo once daily. Year one was a randomized, double blind trial. Year 2 was an open label continuation. DHEA replacement improved glucose tolerance in participants who had abnormal GT initially, reduced plasma triglycerides, and the inflammatory cytokines IL6 and TNFα. © Weiss et al.

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