PLoS ONE

Although many clinical pathological states are now detectable using imaging and biochemical analyses, neuropsychological tests are often considered as valuable complementary approaches to confirm diagnosis, especially for disorders like Alzheimer's or Parkinson's disease, and schizophrenia. The touchscreen-based automated test battery, which was introduced two decades ago in humans to assess cognitive functions, has recently been successfully back-translated in monkeys and rodents. We focused on optimizing the protocol of three distinct behavioral paradigms in mice: two variants of the Paired Associates Learning (PAL) and the Visuo-Motor Conditional Learning (VMCL) tasks. Acquisition of these tasks was assessed in naive versus pre-trained mice. In naive mice, we managed to define testing conditions allowing significant improvements of learning performances over time in the three aforementioned tasks. In pre-trained mice, we observed differential acquisition rates after specific task combinations. Particularly, we identified that animals previously trained in the VMCL paradigm subsequently poorly learned the sPAL rule. Together with previous findings, these data confirm the feasibility of using such behavioral assays to evaluate the power of different models of cognitive dysfunction in mice. They also highlight the risk of interactions between tasks when rodents are run through a battery of different cognitive touchscreen paradigms

Loss of STOP Protein Impairs Peripheral Olfactory Neurogenesis

International audienceIn conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia

Deletion of CB2 cannabinoid receptor induces schizophrenia-related behaviors in mice

The possible role of the CB2 receptor (CB2 r) in psychiatric disorders has been considered. Several animal models use knockout (KO) mice that display schizophrenia-like behaviors and this study evaluated the role of CB 2 r in the regulation of such behaviors. Mice lacking the CB 2 r (CB2 KO) were challenged in open field, light-dark box, elevated plus-maze, tail suspension, step down inhibitory avoidance, and pre-pulse inhibition tests (PPI). Furthermore, the effects of treatment with cocaine and risperidone were evaluated using the OF and the PPI test. Gene expression of dopamine D2 (D2 r), adrenergic-α 2C (α 2C r), serotonergic 5-HT 2A and 5-HT 2C receptors (5-HT 2A r and 5-HT 2C r) were studied by RT-PCR in brain regions related to schizophrenia. Deletion of CB 2 r decreased motor activity in the OF test, but enhanced response to acute cocaine and produced mood-related alterations, PPI deficit, and cognitive impairment. Chronic treatment with risperidone tended to impair PPI in WT mice, whereas it normalized the PPI deficit in CB2 KO mice. CB2 KO mice presented increased D2 r and α 2C r gene expressions in the prefrontal cortex (PFC) and locus coeruleus (LC), decreased 5-HT 2C r gene expression in the dorsal raphe (DR), and 5-HT 2A r gene expression in the PFC. Chronic risperidone treatment in WT mice left α 2C r gene expression unchanged, decreased D2 r gene expression (15 g/kg), and decreased 5-HT 2C r and 5-HT 2A r in PFC and DR. In CB2 KO, the gene expression of D2 r in the PFC, of α 2C r in the LC, and of 5-HT 2C r and 5-HT 2Ar in PFC was reduced; 5-HT 2C r and 5-HT 2A r gene expressions in DR were increased after treatment with risperidone. These results suggest that deletion of CB2 r has a relation with schizophrenia-like behaviors. Pharmacological manipulation of CB2 r may merit further study as a potential therapeutic target for the treatment of schizophrenia-related disorders. © 2011 American College of Neuropsychopharmacology. All rights reserved.This research was supported by grants from the Ministry of Science and Innovation (SAF 2008-01106) and Ministry of Health (RETICS RD06/0001/1004 and PNSD 2007/061) to JM. AOA is a postdoctoral fellow of ‘Fundación para la Investigación Sanitaria en Castilla La Mancha’ (FISCAM).Peer Reviewe