Oxytocin regulation of social transmission of fear in zebrafish reveals its evolutionary conserved role in emotional contagion

Emotional contagion is the most ancestral form of empathy that relies on simple perception-action mechanisms, on top of which more complex forms of empathic behaviors, such as consolation and helping, have evolved. Here we tested to what extent the proximate mechanisms of emotional contagion are evolutionary conserved by assessing the role of oxytocin, known to regulate empathic behaviors in mammals, in social fear contagion in zebrafish, which represents an evolutionary divergent line to that of tetrapods, within vertebrates. Using mutants for the ligand of the fish oxytocin nonapeptide and both of its receptors in zebrafish we showed that oxytocin is necessary for observer zebrafish to copy the distressed behavior of conspecific demonstrators. Exogeneous administration of oxytocin to the ligand mutant rescued the ability of observers to express social fear transmission, indicating that oxytocin is not only necessary but also sufficient for emotional contagion. The brain regions in the ventral telencephalon that are associated with emotional contagion in zebrafish are homologous to those known to be involved in the same process in rodents (e.g. striatum, lateral septum), and receive direct projections from oxytocinergic neurons located in the preoptic area. Finally, we ruled out the hypothesis that social transmission of fear in zebrafish merely relies on behavior contagion by motor imitation, and we showed that it rather relies on emotion discrimination. Together our results support an evolutionary conserved role for oxytocin as a key regulator of basic empathic behaviors across vertebrates.

Effect of amisulpride, olanzapine, quetiapine, and aripiprazole single administration on c-Fos expression in vasopressinergic and oxytocinergic neurons of the rat hypothalamic supraoptic nucleus

Objective. The goal of this study was to reveal the impact of four types of atypical antipsychotics including amisulpride (AMI), olanzapine (OLA), quetiapine (QUE), and aripiprazole (ARI), with different receptor-affinity profile and dissociation constant, on the activity of hypothalamic supraoptic nucleus (SON) vasopressinergic and oxytocinergic neurons.Methods. Male Sprague Dawley rats received a single injection of vehicle (VEH) (0.1 ml/100g), AMI (20 mg/kg), OLA (5 mg/kg), QUE (15 mg/kg/) or ARI (10 mg/kg). Ninety min after treatment, the animals were fixed by transcardial perfusion, the brains removed, and cryocut into serial coronal sections of 35 µm thickness. The sections were processed for c-Fos staining using an avidin-biotin-peroxidase complex and visualized by nickel intensified diaminobenzidine to reach black end product. Afterwards, the sections were exposed to vasopressin (AVP) and oxytocin (OXY) antibodies and the reaction product visualized by biotin-labeled fluorescent Alexa Fluor 568 dye. The data were evaluated from c-Fos and AVP or OXY merged sections.Results. The present study shows that all four antipsychotics applied induced c-Fos expression in the SON. With respect to the stimulation efficacy of the individual antipsychotics, estimated based on the quantity of c-Fos-labeled AVP and OXY neurons, could be a preferential action assigned to QUE over moderate effect of ARI and lower effect to OLA and reduced effect of AMI (VEH < AMI < OLA < ARI < QUE).Conclusion. The present data for the first time provide an insight into the quantitative pattern of brain activity within the clusters of SON AVP and OXY cells in response to different atypical antipsychotics single treatment.

Hindbrain noradrenergic input to the hypothalamic PVN mediates the activation of oxytocinergic neurons induced by the satiety factor oleoylethanolamide

Oleoylethanolamide (OEA) is a gut-derived endogenous lipid that stimulates vagal fibers to induce satiety. Our previous work has shown that peripherally administered OEA activates c-fos transcription in the nucleus of the solitary tract (NST) and in the paraventricular nucleus (PVN), where it enhances oxytocin (OXY) expression. The anorexigenic action of OEA is prevented by the intracerebroventricular administration of a selective OXY receptor antagonist, suggesting a necessary role of OXYergic mediation of OEA's effect. The NST is the source of direct noradrenergic afferent input to hypothalamic OXY neurons, and therefore, we hypothesized that the activation of this pathway might mediate OEA effects on PVN neurons. To test this hypothesis, we subjected rats to intra-PVN administration of the toxin saporin (DSAP) conjugated to an antibody against dopamine-β-hydroxylase (DBH) to destroy hindbrain noradrenergic neurons. In these rats we evaluated the effects of OEA (10 mg/kg, ip) on feeding behavior, on c-Fos and OXY immunoreactivity in the PVN, and on OXY immunoreactivity in the posterior pituitary gland. We found that the DSAP lesion completely prevented OEA's effects on food intake, on Fos and OXY expression in the PVN, and on OXY immunoreactivity of the posterior pituitary gland; all effects were maintained in sham-operated rats. These results support the hypothesis that noradrenergic NST-PVN projections are involved in the activation of the hypothalamic OXY system, which mediates OEA's prosatiety action.