Making available scientific information in the third millennium: perspectives for the neuroscientific community

The rules governing the globalised process of sharing scientific information in the research community are rapidly changing. From the 1950s, commercial publishers started owning a large number of scientific journals and consequently the marketable value of a submitted manuscript has become an increasingly important factor in publishing decisions. Recently some publishers have developed the Open Access (OA), a business scheme which may help stopping such tendency. Indeed, in the case of an open-access publication, the marketable value of a manuscript may be not the primary consideration, since access to the research is not being sold. This may push scientists to re-consider the purpose of peer reviewing. However, costs remain a key point in managing scientific journals because OA method does not eliminate peer review process. Thus, OA may not solve the problem of the market pressures on publishing strategies. Furthermore, the OA has another strong point: everyone can read OA papers, including scientist living in poor countries. But, will OA method create new discriminations on who can publish on OA journals? Will it be possible to really exclude or strongly limit the influences of the market from scientific publishing? The example of the non-profit e-print arXiv (http://arXiv.org/), a fully automated electronic archive and distribution server for research papers with no peer review will be discussed. For neuroscientists, the possibility to make available scientific data, even in the case of negative results (usually, very difficult to publish) is an important step to avoid purposeless repetition of costly experiments involving animal subjects. The possibility to arrange internationally or locally peer reviewed papers in institutional repositories (IR) is a necessity. However, access to IR should be regulated, e.g. banning or limiting profit organizations and exploiting internet systems, professional organizations or network groups

Antidepressant Treatment Outcome Depends on the Quality of the Living Environment: A Pre-Clinical Investigation in Mice

Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). A recent hypothesis posits that the increase in serotonin levels induced by SSRI may not affect mood per se, but enhances neural plasticity and, consequently, renders the individual more susceptible to the influence of the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. Anhedonia, brain BDNF and circulating corticosterone levels, considered endophenotypes of depression, were investigated. Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying higher saccharin preference, higher brain BDNF levels and reduced corticosterone levels. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile, displaying a faster decrease of saccharin preference, lower brain BDNF levels and increased corticosterone levels. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determine

Nonmotor symptoms in Parkinson's disease: Investigating early-phase onset of behavioral dysfunction in the 6-hydroxydopamine-lesioned rat model

To investigate the psychiatric symptoms accompanying the early phases of Parkinson's disease (PD), we injected adult rats with 10.5 μg 6-hydroxydopamine (6-OHDA) bilaterally into the dorsal striatum. The resulting neurodegeneration led, 12 weeks after injection, to a mild (36%) reduction of striatal dopamine. We tested the behavioral response of sham and 6-OHDA-lesioned animals at different time points after injection to evaluate the onset and progression of behavioral abnormalities. The results showed that such a mild reduction of dopamine levels was associated with a decrease in anxiety-like behavior, an increase in "depression"-like behavior, and a marked change in social behavior. Learning and memory abilities were not affected. Overall, the PD rat model used here displays behavioral alterations having face validity with psychiatric symptoms of the pathology and thus appears to be a valuable tool for investigating the neural bases of the early phases of PD. © 2008 Wiley-Liss, Inc

A Trouble Shared Is a Trouble Halved: Social Context and Status Affect Pain in Mouse Dyads

In mice behavioral response to pain is modulated by social status. Recently, social context also has been shown to affect pain sensitivity. In our study, we aimed to investigate the effects of interaction between status and social context in dyads of outbred CD-1 male mice in which the dominance/submission relationship was stable. Mice were assessed for pain response in a formalin (1% concentration) test either alone (individually tested-IT), or in pairs of dominant and subordinate mice. In the latter condition, they could be either both injected (BI) or only one injected (OI) with formalin. We observed a remarkable influence of social context on behavioral response to painful stimuli regardless of the social status of the mice. In the absence of differences between OI and IT conditions, BI mice exhibited half as much Paw-licking behavior than OI group. As expected, subordinates were hypoalgesic in response to the early phase of the formalin effects compared to dominants. Clear cut-differences in coping strategies of dominants and subordinates appeared. The former were more active, whereas the latter were more passive. Finally, analysis of behavior of the non-injected subjects (the observers) in the OI dyads revealed that dominant observers were more often involved in Self-grooming behavior upon observation of their subordinate partner in pain. This was not the case for subordinate mice observing the pain response of their dominant partner. In contrast, subordinate observers Stared at the dominant significantly more frequently compared to observer dominants in other dyads. The observation of a cagemate in pain significantly affected the observer's behavior. Additionally, the quality of observer's response was also modulated by the dominance/submission relationship

Scopolamine effects on ultrasonic vocalization emission and behavior in the neonatal mouse

Developmental alterations of the cholinergic system can lead to short- and long-term detrimental consequences for brain function. In order to study the cholinergic modulation of behavior in the neonatal mouse, we characterized ultrasonic vocalizations and spontaneous behavior of 5- and 8-day old CD-1 Swiss mice after i.p. administration of the muscarinic antagonist scopolamine (doses, 0.8 and 2mg/kg) during both a first isolation of 30 min and a re-isolation of 5min, occurring immediately after a brief reunion with the mother. As concerns the first isolation, on PND 5, only scopolamine 0.8 mg/kg increased the number of ultrasonic vocalizations and, on PND 8, both doses increased it in a dose-dependent fashion. Scopolamine effects on spontaneous behavior were very limited on PND 5, but markedly evident on PND 8, the high dose increasing activity profile. Independently from treatment, the brief reunion with the mother had no effects on mouse ultrasound emission during re-isolation. The present results show that the cholinergic system plays a role in inhibiting rodent pup USV emission and spontaneous behavior and suggest that the analysis of spontaneous behavior and, in particular, of the number of ultrasonic vocalizations represents a valuable tool to detect precocious developmental alterations of the cholinergic function in the mouse, the most used animal species to model human health disorders

Effects of perinatal exposure to a polybrominated diphenyl ether (PBDE 99) on mouse neurobehavioural development

Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, are extensively diffused in the environment as shown by several studies on sentinel animal species, as well as humans. Of particular concern are the reported high levels of PBDEs in human milk, as almost no information is available on their potential effects on developing organisms. We investigated the effects of perinatal PBDE exposure on mouse neurobehavioural development. 2,2',4,4,5-pentabromodiphenylether (PBDE 99; 0.6, 6 and 30 mg/kg per day) was administered daily to CD-1 Swiss females by gavage from gestational day (GD) 6 to postnatal day (PND) 21. Aroclor 1254 (A1254; 6 mg/ kg per day), a PCB mixture, was administered following the same schedule and served as a positive controL The PBDE 99 medium dose had an effect on litter viability. Sensori-motor development analysis (PNDs 2-20) revealed a delayed appearance of climbing response in the PBDE 99 high-dose group. On PND 11, the homing test revealed a trend for treated animals, particularly the A1254 group, to be more active than controls. This activity level alteration was strongly increased on PNDs 34 and 60 in an open-field arena. On PND 60, treated mice showed also an altered thigmotaxis, spending more time in the centre of the arena than controls. At adulthood, A1254 treated mice were still hyperactive, whereas the PBDE 99 groups tended to be hypoactive. These findings showed that perinatal exposure to PBDE 99 produces several behavioural alterations and that its effects are not always similar to those of A1254. The possibility of exposure of neonates to PBDEs warrants further studies to characterise their developmental neurotoxicity

Polybrominated diphenyl ethers: Neurobehavioral effects following developmental exposure

Polybrominated diphenyl ethers (PBDEs), a class of widely used flame retardants, are becoming widespread environmental pollutants, as indicated by studies on sentinel animal species, as well as humans. Of particular concern are the reported increasingly high levels of PBDEs in human milk, as should be given that almost no information is available on their potential effects on developing organisms. In order to address this issue, studies have been conducted in mice and rats to assess the potential neurotoxic effects of perinatal exposure to PBDEs (congeners 47, 99, 153 and the penta-BDE mixture DE-71). Characteristic endpoints of PBDE neurotoxicity are, among others, endocrine disruption (e.g. decreased thyroid hormone levels), alteration in cholinergic system activity (behavioral hyporesponsivity to nicotine challenge), as well as alterations of several behavioral parameters. In particular, the main hallmark of PBDE neurotoxicity is a marked hyperactivity at adulthood. Furthermore, a deficit in learning and memory processes has been found at adulthood in neonatally exposed animals. Some of neurotoxic effects of PBDEs are comparable to those of polychlorinated biphenyls (PCBs), though the latter class of compounds seems to exert a stronger toxic effect. Available information on PBDE neurotoxicity obtained from animal studies and the possibility of neonatal exposure to PBDEs via the mother's milk suggest that these compounds may represent a potential risk for neurobehavioral development in humans. © 2003 Elsevier Science Inc. All rights reserved