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International audience; We explored here the hypothesis that temporary chronic water restriction in mice affects social behavior, via its action on the density of 5-HT neurons in dorsal and median raphe nuclei (DRN and MRN). For that, we submitted adult C57BL/6J mice to mild and controlled temporary dehydration, i.e., 6h of water access every 48h for 15 days. We investigated their social behavior in a social interaction task known to allow free and reciprocal social contact and to rely on prefrontal cortex activity and monoaminergic prefrontal input. Results showed that temporary dehydration increases significantly time spent in social contact and social dominance. It also expands 5-HT neuron density within both DRN and MRN and the behavioral and neuronal plasticity were positively correlated. Our findings suggest that disturbance in 5-HT innervation caused by temporary dehydratation stress unbalances choice processes of animals in social context.

International audience; Autism spectrum disorder (ASD) is characterized by early onset of behavioral and cognitive alterations. Low plasma levels of oxytocin (OT) have also been found in ASD patients; recently, a critical role for the enzyme CD38 in the regulation of OT release was demonstrated. CD38 is important in regulating several Ca 2+-dependent pathways, but beyond its role in regulating OT secretion, it is not known whether a deficit in CD38 expression leads to functional modifications of the prefrontal cortex (PFC), a structure involved in social behavior. Here, we report that CD38 2/2 male mice show an abnormal cortex development, an excitation-inhibition balance shifted toward a higher excitation, and impaired synaptic plasticity in the PFC such as those observed in various mouse models of ASD. We also show that a lack of CD38 alters social behavior and emotional responses. Finally, examining neu-romodulators known to control behavioral flexibility, we found elevated monoamine levels in the PFC of CD38 2/2 adult mice. Overall, our study unveiled major changes in PFC physiologic mechanisms and provides new evidence that the CD38 2/2 mouse could be a relevant model to study pathophysiological brain mechanisms of mental disorders such as ASD.-Martucci, L. A multiscale analysis in CD38-/-mice unveils major prefrontal cortex dysfunctions.

International audience; Following the cloning and sequencing of the A subunit of the 5-HT3 receptor, two alternatively spliced isoforms, 5-HT3-AS and 5-HT3-AL, have been identified. In order to analyse the distribution of the receptor, a polyclonal antibody has been produced against the short form which is the most abundant in the central nervous system [Doucet et al. (2000) Neuroscience 95, 881-892]. As expected from the recognition of functional 5-HT3 receptors, immunostaining by this anti-5-HT3-R-AS antibody matched the distribution of the high-affinity 5-HT3 binding sites in the rat brain and spinal cord. 5-HT3-AS-like immunoreactivity was detected at low levels in the limbic system, particularly in the amygdala and the hippocampus, and in the frontal, piriform and entorhinal cortices. High levels of immunoreactivity were found in the brainstem, mainly in the nucleus tractus solitarius and the nucleus of the spinal tract of the trigeminal nerve, and in the dorsal horn of the spinal cord. At the ultrastructural level, immunostaining was generally found associated with axons and nerve terminals (70-80%) except in the hippocampus, where labelled dendrites were more abundant (56%). This preferential localization on nerve endings is consistent with the well-documented physiological role of 5-HT3 receptors in the control of neurotransmitter release. However, the different distribution in the hippocampus raises the question of whether differential addressing mechanisms exist for preferentially targeting 5-HT3 receptors to postsynaptic dendritic sites as compared to presynaptic nerve endings, depending on the nature of the neurons bearing these receptors.

International audience; In the present study, we examined the possibility of the presence of the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) system in the rat heart as well as the effects of drugs affecting noradrenergic transmission upon the cardiovascular responses elicited by peripheral administration of NPFF. The presence of NPFF receptors on heart sections and of NPFF-immunoreactivity in heart tissue was demonstrated with autoradiographic and radioimmunoassay procedures, respectively. Intravenous administration of NPFF (100-300 micrograms/kg) produced a dose-dependent increase in blood pressure and heart rate without affecting plasma noradrenaline and adrenaline levels. These effects of NPFF were also observed, although attenuated, in catecholamine-depleted rats and in rats pretreated with a ganglionic blocking agent, hexamethonium (10 mg/kg, i.v.). Prazosin (100 micrograms/kg, i.v.), an alpha1 adrenergic receptor antagonist, reduced the NPFF-induced blood pressure response by 50%. In contrast, propranolol (2 mg/kg, i.v.) and metroprolol (0.5 mg/kg, i.v.), beta- and beta1 adrenergic receptor antagonists, respectively, reduced the NPFF-induced heart rate response by 50%. Surprisingly, the alpha2 adrenergic receptor antagonists, idazoxan (2 mg/kg, i.v.) and yohimbine (2 mg/kg, i.v.), both produced a drastic increase in the NPFF-induced heart rate response. These data, which demonstrate the presence of the NPFF system in the rat heart, suggest that the cardiovascular responses of peripheral administration of NPFF are mediated by the stimulation of peripheral NPFF receptors. In addition, the present data show that the aforementioned NPFF-induced responses are also mediated by catecholamine-dependent mechanisms and suggest a functional interaction between adrenergic and NPFF systems.