The cortico-medial amygdala in the central nervous system organization of agonistic behavior

Previous studies suggested that the corticomedial amygdala is involved in agonistic behavior by affecting social learning processes. The present study shows that deficits in the avoidance of a dominant male rat conditioned by defeat were only observed after bilateral lesions restricted to the medial amygdala and not after destroying the cortical portion. These results are related to the specific afferent and efferent connections of the medial amygdala with other brain structures involved in the control of agonistic behavior. Within the corticomedial amygdala the medial amygdaloid nucleus was found to be a major recipient of afferents from the accessory olfactory bulb, but also a source of efferent projections to the ventrolateral aspects of the ventromedial hypothalamic nucleus and the ventral premammillary nucleus. A strong reciprocity exists in the connections between ventromedial hypothalamus and premammillary nuclei with the medial amygdala. The connections between the ventromedial hypothalamic and dorsal premammillary nucleus with the midbrain periaqueductal grey suggest an important role for the periaqueductal gray in the descending output in the anatomical substrate for agonistic behavior

The Novel Antidepressant Agomelatine Normalizes Hippocampal Neuronal Activity and Promotes Neurogenesis in Chronically Stressed Rats

Agomelatine is a novel antidepressant which acts as a melatonergic (MT1/MT2) receptor agonist and serotonergic (5-HT2C) receptor antagonist. The antidepressant properties of agomelatine have been demonstrated in animal models as well as in clinical studies. Several preclinical studies reported agomelatine-induced effects on brain plasticity, mainly under basal conditions in healthy animals. Yet, it is important to unravel agomelatine-mediated changes in the brain affected by psychopathology or exposed to conditions that might predispose to mood disorders. Since stress is implicated in the etiology of depression, it is valid to investigate antidepressant-induced effects in animals subjected to chronic stress. In this context, we sought to determine changes in the brain after agomelatine treatment in chronically stressed rats. Adult male rats were subjected to footshock stress and agomelatine treatment for 21 consecutive days. Rats exposed to footshock showed a robust increase in adrenocorticotropic hormone (ACTH) and corticosterone. Chronic agomelatine treatment did not markedly influence this HPA-axis response. Whereas chronic exposure to daily footshock stress reduced c-Fos expression in the hippocampal dentate gyrus, agomelatine treatment reversed this effect and normalized neuronal activity to basal levels. Moreover, chronic agomelatine administration was associated with enhanced hippocampal cell proliferation and survival in stressed but not in control rats. Furthermore, agomelatine reversed the stress-induced decrease in doublecortin expression in the dentate gyrus. Taken together, these data show a beneficial action of agomelatine in the stress-compromised brain, where it restores stress-affected hippocampal neuronal activity and promotes adult hippocampal neurogenesis.