Ocytocine et attachement homo et hétéro-spécifique: rôle dans l'isolement et l'apaisement social – BOND.007

The neurobiological bases of filial attachment are still poorly known, in contrast to the extensive work done on maternal behaviour. Sheep are precocial mammals developing mutual mother-young recognition. The fact that lambs can develop a strong bond with their dam makes them suitable for the study of filial attachment. Lambs have the ability to bond both to their dam and to humans but the neurobiological mechanism may be dissimilar. As OT is known to play a major role in social behaviours, the aim of our project is to examine to what extend the OXTergic system participates in the physiological and neurobiological mechanism mediating homo- and hetero-specific attachment responses. We hypothesise that the release of OXT will be triggered by the mere presence of the mother, but that in the case of the humans, additional somatosensory stimulation such as touch will be necessary. Such additional stimulation from the mother (nosing, body contact) should also potentiate the release of OXT. We will use the separation-reunion paradigm developed by Ainsworth (1989) in human infants and adapted for animals. Under such experimental conditions, subjects are soothed by the presence of their partner and distressed when isolated. In addition, knowing that (i) positive interactions with the attachment figure promotes calmness and (i) OXT is proposed as a mediator for well-being, we will test the hypothesis that calming stimuli provided by the attachment figure decrease heart rate and cortisol levels, activate specific brain structures, and that most of the behavioural and physiological responses can be attenuated by OXT antagonists. General experimental situation ' At birth, lambs will be either left with their mother or they will be separated and reared artificially with powdered milk. In the second situation, a specific person will take care of a specific group of lambs to favour the development of hetero-specific attachment. ' On week 1, lambs will be submitted to a two-choice test in order to determine the existence of a preference for the attachment figure (ewe or human). ' On week 2, neurosurgery will be performed on lambs used in Task.1 to implant an intracerebroventricular cannula for subsequent collection of cerebrospinal fluid. ' On week 4 to 6, lambs will be allocated to one of the three following groups: o (i) tested with their attachment figure (no somatosensory stimulation), then isolated, and lastly tested after reunion with the attachment figure (no somatosensory stimulation). Each phase of the test lasts 30 min making a total of 90 min for the whole testing session. Proximal interaction will be prevented by a double layer fence (50 cm apart), the human will sit still. Main hypothesis: OXT is more likely to be released in the presence of the mother; o (ii) tested in the same situation as above but with somatosensory stimuli provided by the attachment figure (both partners can interact: body-to-body contact with mother, nosing, sniffing; stroking with human). Main hypothesis: OXT is released in both cases, response potentiated by nosing/stroking in comparison to previous situation. o (iii) tested in isolation. Main hypothesis: no change in OXT levels; o These three situations may be repeated according to experimental needs. Specific aims of the proposal ' Task 1. Subtask 1.1 is a crucial descriptive step that will give valuable correlative information between central-peripheral OXT release and (1) the distressed state induced by isolation, (2) the calm state induced by the mere presence of the attachment figure, (3) the calm stated induced by somatosensory stimuli provided during positive interactions with the attachment figure (and plasma cortisol and heart rate variation). Subtask 1.2 will characterize neuronal activation during interactions with the attachment figure which will include, or not, additional somatosensory stimulation (mother: nosing; human: stroking). ' Task 2 will aim at determining the sites and dynamic of action of OXT with the use of gamma cameras and scintigraphy. ' Task 3 will aim at quantifying in deeper details the behavioural responses of lambs when interacting with their attachment figure. Based on results from Subtask 1.1, specific times in regards to the separation-reunion situation will be chosen to take blood samples and correlate OXT, cortisol levels, and heart rate variation with the intensity of the interactions. ' Task 4 will test the hypothesis of the involvement of the OXTergic system in the expression of calmness. The effects of the antagonist will be tested when lambs will be with their attachment figure. Social bonds, e.g. the relationship between the responses displayed by lambs in the absence or the presence of their attachment figure and OXT will be studied with an interdisciplinary approach at 7 levels: 1) Behaviour 2) Physiology; 3) Neurophysiology 4) Neuroendocrinology 5) Neurobiology 6) Functional brain imaging 7) Pharmacology