Dichlobenil-induced limited damage of the olfactory system alter exploratory and social behaviour in the mouse

Damages to the olfactory system may cause behavioural modulation not limited to the sensory sphere. Ablation of olfactory bulbs in rodents induces a behavioural pattern with striking modifications in different behavioural domains, that may be rescued by antidepressant agents. A similar pattern was described also after peripheral destruction of the olfactory epithelium (OE, see Mucignat-Caretta et al. Neurobiol. Dis., 2004, 16, 386). In the present series of experiments, the intraperitoneal injection of 2,6-Dichlorobenzonitrile induced a selective lesion in the OE of male Swiss mice restricted to the dorsomedial zone (zone I of OE), as revealed by a thinner histological appearance. The lesion was confirmed by immunohistochemistry of the OE and olfactory bulbs, showing modifications in a variety of markers, including cAMP-dependent protein kinases, Olfactory Marker Protein and Tyrosine-hydroxylase in the OE zone I or in its projections to dorsomedial glomeruli in the olfactory bulb. Modifications were also present in the subventricular zone and rostral migratory stream. A week after the injection, mice were tested for a variety of behavioural domains modulated by olfactory system, including exploratory, aggressive and anxious behaviours. Mice were anosmic, as shown by their inability to find a hidden piece of food. However, a reduction in the exploratory behaviour was also demonstrated in the open field test. Concerning social interactions, the olfactory lesioned mice attacked a male adult intruder mouse, similarly to control mice, but also increased the interspecific predatory aggression, similarly to olfactory bulb-lesioned mice. In conclusion, selective damages limited to zone I of OE are sufficient to induce some changes in the olfactory bulb circuitry that ultimately result in behavioural changes, similar to complete OE lesions. These data suggest a selective action of deafferentation on olfactory bulb output to limbic areas involved in behavioural modulation.