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The use of oncolytic viruses is an innovative approach to lyse tumor cells and induce antitumor immune responses. Eight dogs diagnosed with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15, an oncolytic canine adenovirus (CAV). To evaluate the treatment's safety, a blood count, biochemistry, and coagulation test were performed before treatment and during follow-up. Immune populations were analyzed by flow cytometry. Anti-adenovirus antibodies were also determined. The immune infiltration, vascularization, and viral presence in the tumor were determined by CD3, CD4, CD20, CD31 and CAV by immunohistochemistry. All the dogs maintained a good quality of life during follow-up, and some had increased median survival time when compared with dogs treated with chemotherapy. No treatment-related adverse effects were detected. The Response Evaluation Criteria In Solid Tumors criteria were also assessed: two patients showed a partial response and the rest showed stable disease at various times during the study. ICOCAV15 was detected inside the tumor during follow-up, and antiviral antibodies were detected in all patients. Furthermore, the tumor-infiltrating immune cells increased after viral administration. Therefore, we suggest that intratumorally administered ICOCAV15 could represent as a new tool for the treatment of canine carcinoma because it is safe, well-tolerated by dogs, and shows promising results.

Meta-analyses reveal that behavioral differences between liars and truth tellers are small. To facilitate lie detection, researchers are currently developing interviewing approaches to increase these differences. Some of these approaches assume that lying is cognitively more difficult than truth telling; however, they are not based on specific cognitive theories of lie production, which are rare. Here we examined one existing theory, Walczyk et al.'s (2014) Activation-Decision-Construction-Action Theory (ADCAT). We tested the Decision component. According to ADCAT, people decide whether to lie or tell the truth as if they were using a specific mathematical formula to calculate the motivation to lie from (a) the probability of a number of outcomes derived from lying vs. telling the truth, and (b) the costs/benefits associated with each outcome. In this study, participants read several hypothetical scenarios and indicated whether they would lie or tell the truth in each scenario (Questionnaire 1). Next, they answered several questions about the consequences of lying vs. telling the truth in each scenario, and rated the probability and valence of each consequence (Questionnaire 2). Significant associations were found between the participants' dichotomous decision to lie/tell the truth in Questionnaire 1 and their motivation to lie scores calculated from the Questionnaire 2 data. However, interestingly, whereas the expected consequences of truth telling were associated with the decision to lie vs. tell the truth, the expected consequences of lying were not. Suggestions are made to refine ADCAT, which can be a useful theoretical framework to guide deception research., (Copyright © 2016 Elsevier B.V. All rights reserved.)

5-Hydroxytryptamine (5-HT) is an important neurotransmitter mediating many aspects of cognition and behaviour. One psychology in which 5-HT plays an important role is impulsive responding. Recently, we have demonstrated that variation in an aspect of impulsive behaviour, namely delayed gratification, has a clear genetic contribution. Here, we examined the neurobiological relevance of a recently discovered single nucleotide polymorphism (SNP) in the murine gene tryptophan hydroxylase (mTph2) by analysing extracellular levels of 5-HT in medial prefrontal cortex (mPFC) and ventral striatum (VS), key brain regions for impulsive behaviours. The allelic variants were associated with systematic effects on baseline 5-HT efflux in the mPFC and VS. We then went on to examine whether the mTph2 allelic variants gave rise to differences in impulsive behaviour. However, the mTph2 genotype, and therefore presumably baseline brain levels of 5-HT, did not predict impulsive choice, as indexed by sensitivity to delayed reinforcement. Consequently, the data do not support a role for the mTph2 C1473G polymorphism on this aspect of impulsive behaviour. Instead, they indicate that perturbations of the 5-HT system via heritable traits may have differential consequences for qualitatively distinct aspects of impulsive behaviour.

Ozone exposure, depending on the dose, is a noninvasive model of oxidative stress. The purpose of this work was to study striatal damage and cell death induced by oxidative stress. Sixty-three male Wistar rats were divided into two groups--Group 1: animals were exposed to an air stream free of ozone for 4 h; and Group 2: animals were exposed to 1 ppm of ozone for 4 h. Four subgroups in each treatment group were then tested 3 h after control or ozone exposure for: (1) exploratory and freezing behavior; (2) lipid peroxidation levels; (3) in vivo release of amino acid and monoamine transmitters, and metabolites and nitric oxide; and (4) striatal ultrastructural changes. Results showed that the ozone decreased exploratory and increased freezing behaviors. It also increased striatal lipoperoxidation levels and basal dopamine, glutamate, and nitric oxide (arginine, citrulline, and nitrate used as indices) concentrations and decreased those of 5-HT. Concentrations of GABA were initially decreased 3 h after ozone but then were increased 3 and 5 days afterwards. Increased lipofucsine, neuronal cytoplasm and dendrite vacuolation, and dilation of rough endoplasmic reticulum cisterns and dark cells were observed in striatal medium spiny neurons in ozone-exposed rats. These alterations suggest a neurodegenerative process caused by oxidative stress after acute ozone exposure.

Dopamine has been implicated in the control of sexual behaviour, but its role seems quite complex and controversial. The aim of the present experiments was to investigate the effects of dopamine (DA) acting on D2 receptors in the mediobasal hypothalamus (MBH) on sexual behaviour in female sheep. To achieve this, the D2 agonist, quinpirole, was administered bilaterally via microdialysis probes into the MBH of ovariectomized ewes either before or after oestradiol (E2) administration. Quinpirole (100 ng/ml) infused for 6 h just before E2 hastened the onset of oestrus behaviour and the luteinizing hormone surge, whereas the same treatment given 6-12 h or 18-21 h after E2 decreased the intensity of sexual receptivity without affecting LH or prolactin secretion. We then tested the hypothesis that E2 stimulates the onset of oestrus partly by decreasing DA activation of D2 receptors. In this case the D2 antagonists pimozide or spiperone (100 ng/ml) were infused into the MBH via microdialysis probes for 11 h in the absence of E2 administration. A significant number of ewes showed induction of receptivity with both antagonists, although its intensity was significantly lower than that induced by E2. These treatments generally did not significantly alter extracellular concentrations of monoamines or aminoacids although quinpirole modulated the ability of sexual interactions to increase noradrenaline release. These experiments show that DA acts via D2 receptors in the MBH to control female sexual behaviour in a biphasic manner: the onset of sexual motivation and receptivity requiring an initial increase in activation followed by a decrease. This dual action could explain some of the controversies concerning DA action on sexual behaviour.

The effects of vaginocervical stimulation (VCS) on glutamate (GLU), aspartate (ASP), gamma-aminobutyric acid (GABA), noradrenaline (NA), arginine (ARG) and nitric oxide (NO) (citrulline) release in the nucleus of the solitary tract (nTS) were measured in anaesthetised female rats as a function of the oestrus cycle. During pro-oestrus/oestrus (P/E), but not during met-oestrus/di-oestrus (M/D), VCS significantly increased concentrations of NA, ASP, GLU, NO (citrulline) and GABA, but not ARG. Basal NA concentrations were also increased in P/E. These effects were prevented by bilateral section of either the vagus nerve or pelvic and hypogastric nerves. Vagotomy also significantly decreased basal NO concentrations in M/D and P/E while pelvic and hypogastric nerve section significantly increased GABA concentrations. Our results therefore confirm that the nTS is a relay structure for the visceral afferents sending information from the uterus into the central nervous system. The ability of VCS to trigger classical transmitter release and NO in the female is influenced by the stage of the oestrous cycle and is routed both via the vagus and pelvic/hypogastric nerves.

In vivo microdialysis was used to investigate the effects of ovariectomy and the oestrus cycle on vaginocervical stimulation-evoked classical transmitter and nitric oxide release in the olfactory bulb of anaesthetized (urethane) and conscious rats. During pro-oestrus/oestrus, vaginocervical stimulation (1 or 10 min) significantly increased concentrations of glutamate, aspartate, GABA, noradrenaline, dopamine and nitric oxide (citrulline) but failed to do so in met-oestrus/di-oestrus or following ovariectomy. Potassium chloride-evoked GABA, noradrenaline and nitric oxide release in the olfactory bulb was also significantly enhanced during pro-oestrus/oestrus. The effects of vaginocervical stimulation on olfactory bulb transmitter release during pro-oestrus/oestrus were significantly reduced by pelvic or vagus nerve section. Basal concentrations of classical transmitters and nitric oxide in the olfactory bulb did not vary across the oestrus cycle although noradrenaline and dopamine levels were reduced following ovariectomy. These results confirm our previous electrophysiological data showing that the olfactory bulb mitral cells are only excited by vaginocervical stimulation during pro-oestrus/oestrus. They also suggest that sex hormones acting primarily at the level of the olfactory bulb dramatically enhance the ability of vaginocervical stimulation to evoke release of both classical transmitters and nitric oxide in this region. Such alterations in neurochemical release in the olfactory bulb may be important for mediating plasticity changes underlying olfactory recognition of mates or offspring.

The effects of N-methyl-D-aspartate (NMDA), kainate, S-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and KCl on striatal nitric oxide (NO), acetylcholine (ACh), dopamine (DA), serotonin (5-HT), aspartate (ASP), glutamate (GLU) and gamma-aminobutyric acid (GABA) release were measured in anaesthetized rats in vivo by microdialysis and in vitro in organotypic slice cultures. Local NMDA (1-100 microM) infusion by retrodialysis dose-dependently increased levels of classical transmitters, NO2-, NO3-, citrulline and arginine at similar thresholds (10 microM). Similar patterns of NMDA-evoked (50 microM) release were seen in striatal cultures. NMDA-evoked changes were all calcium-dependent and blocked by NMDA (APV or MK-801) but not AMPA/kainate (DNQX) receptor antagonists, excepting DA which could be prevented by both. In vivo, kainate increased NO2-, NO3-, CIT and ARG levels at 50 and 100 microM but was less potent than NMDA. Kainate also evoked significant ACh, DA and GLU release dose-dependently starting at 1-10 microM whereas 5-HT, ASP and GABA required 50 or 100 microM doses. Kainate effects were inhibited by DNQX, but not by APV, and were calcium-dependent, AMPA failed to alter NO2-, NO3-, CIT or ARG levels at 50 or 100 microM doses but dose-dependently increased ACh and DA. Similar results were seen with kainate (50 microM) and AMPA (50 microM) in vitro. KCl evoked NO2-, NO3-, CIT and ARG release as well as that of the classical transmitters in vivo and in vitro. In vivo administration of the NO synthase inhibitor L-nitroarginine (L-NARG; 100 microM) significantly reduced NO2-, NO3- and CIT levels and prevented NMDA, kainate or KCl-evoked increases. It also potentiated ACh, ASP, GLU and GABA release and reduced that of DA in response to 50 microM NMDA whereas treatment with an NO-donor (SNAP; 10 microM) significantly reduced evoked ACh, ASP and GLU release. The NO synthase inhibitor L-NARG potentiated kainate-evoked ACh release and reduced that of DA, although less potently than NMDA, but it had no effect on KCl-evoked transmitter release. Overall, these results show that both NMDA and kainate increase striatal NO release at similar dose-thresholds as for classical transmitter release suggesting that NO is dynamically released under physiological and not just pathological conditions. Reductions of striatal NO levels also potentiates calcium-dependent transmitter release in response to NMDA and, to a lesser extent, kainate, whereas increasing them reduces it. This is consistent with a role for NO as a neuroprotective agent in this region acting to desensitize NMDA receptors.

The noradrenergic innervation of the rat thymus during pregnancy and the post partum period was examined by a sucrose glyoxylic acid method for catecholamines, and by high pressure liquid chromatography. Fluorescent nerves decreased in number throughout pregnancy when there was an overall loss in thymic weight due to cortical involution. These changes are maximal by parturition. There was a dramatic increase in nerves between d 21 of pregnancy and d 1 after parturition, especially in the capsule and around blood vessels in the connective tissue septa. The neonates were removed at parturition and thymic weight was rapidly regained. The increased numbers of nerves remained throughout this post partum period. Noradrenaline levels in the thymus altered in a similar pattern throughout pregnancy and the post partum period, but did not parallel thymic weight changes. The mean noradrenaline concentration in the virgin thymus was 1063 +/- 107 pg/mg protein. Levels remained similar during early pregnancy and increased significantly at d 16. Virgin levels were regained by d 21. Values peaked after parturition but rapidly decreased over the next 3 days, and remained at or below virgin levels to d 28 except for a transient rise at d 10 post partum. Adrenaline values were consistently below detection levels. This study shows that there are variations in both nerves visualised, and in neurotransmitter (noradrenaline) content in the thymus during the course of pregnancy and the post partum period. Thus thymic function could be influenced by central events (levels of catecholamines in peripheral blood) as well as local events mediated by transmitter changes in nerves.

Adult wether sheep (n = 8) were subjected to 60 minutes of psychological (isolation) or physical (transport simulation/standing in water) stress, or a control handling procedure in the home pen. Blood samples were taken before and during these treatments and the plasma concentrations of cortisol, prolactin, noradrenaline and adrenaline determined. All the stressors significantly increased plasma cortisol concentrations (P < 0.001) whereas only transport simulation increased prolactin secretion (P < 0.005). Noradrenaline concentrations showed little change in response to the various treatments, with the exception of isolation which produced a small non-significant increase (P < 0.08). All the stress procedures stimulated adrenaline release within the first 10 minutes but the most marked effects were seen after transport simulation and isolation, both of which induced a significant increase throughout the treatment period (P < 0.01).

Cultures of mouse hypothalamus from embryonic day 15 fetuses were exposed to kainic acid (KA) to study effects on survival of selected cell populations. After 6 days in vitro, immunocytochemistry revealed destruction of dopaminergic and GABAergic neurones after KA-treatment, whereas numbers of oxytocinergic cells and neurones containing metEnkephalin were unchanged. Surviving neurones were characterized by a loss of processes or a reduction of process length. Glial cell numbers did not show any differences between groups. Amino acid concentrations decreased after KA-treatment; only glutamine and taurine levels were unaffected. We conclude that toxic effects of KA differ with respect to distinct neuronal populations of the mouse hypothalamus. Therefore, experimental data concerning neuronal destruction under in vitro conditions have to take into account the selectivity of this neurotoxic agent.

Young pigs, which are useful experimental animals for biomedical research, were prepared with lateral intracerebroventricular (ICV) cannulae and housed individually in cages fitted with operant panels, with food and water ad lib. ICV injection of 200 micrograms of dynorphin A 1-17 or 1-13 resulted in a significant meal commencing within 2-5 min. Shorter fragments of dynorphin (1-10, 1-9, 1-8) were ineffective at inducing feeding as was dynorphin B (rimorphin). In the same situation, leumorphin and alpha neo-endorphin (200 micrograms) elicited significant feeding but beta neo-endorphin did not. Dynorphin 1-17 or 1-13, administered 5 min before feeding started, increased meal size when pigs were fed after 4-h deprivation. Naloxone ICV (0.4 mg) significantly reduced food intake in pigs feeding after 4-h deprivation and its main effect was in the second half of the meal. Naloxone also abolished the effect of ICV dynorphin. It is concluded that dynorphin and related endogenous opioids are involved in the regulation of food intake in pigs.

A method is described for the automatic sampling of CSF from conscious freely moving rats and the simultaneous determination of 5-HIAA and HVA by high-pressure liquid chromatography with electrochemical detection (HPLC-EC). Timed samples (30 microliters) were taken directly from a chronically implanted cannula in the cisterna magna of adult female rats by the HPLC autoinjector. The low volume of sample permitted withdrawal of repeated samples without cross-contamination. The cannula could be used the day after implantation and remained patent for at least two weeks. Treatment with probenecid (200 mg/kg i.p.) caused an increase of both metabolites in the CSF. Pargyline (50 mg/kg i.p.) affected both the 5-HT and dopaminergic systems, reducing their metabolite levels. alpha-Methyl-p-tyrosine (200 mg/kg i.p.) acted selectively on the catecholaminergic system lowering HVA levels. The method accurately measured amine metabolite changes in the CSF due to pharmacological manipulations.