Post-weaning social isolation attenuates c-Fos expression in GABAergic interneurons in the basolateral amygdala of adult female rats.

Previous studies have found that adolescent social isolation of rats can lead to an increased anxiety state during adulthood, while chronic anxiety states are associated with dysregulated local GABAergic inhibition within the basolateral amygdala (BL). Therefore, we investigated the effects of post-weaning social isolation of female rats, in combination with a challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142), on a subset of GABAergic interneurons in the BL in adulthood using dual immunohistochemical staining for c-Fos and parvalbumin. Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-housed for an additional 2 weeks. Group-reared rats and isolation-reared rats injected with FG-7142 had increased c-Fos expression in GABAergic interneurons in the anterior part of the BL compared to group-reared rats and isolation-reared rats, respectively, injected with vehicle. Isolation rearing had a main effect to decrease c-Fos expression in GABAergic interneurons in the anterior part of the BL compared to group-reared rats. These data suggest that post-weaning social isolation of female rats leads to dysregulation of a parvalbumin-containing subset of local GABAergic interneurons in the anterior part of the BL, which have previously been implicated in the pathophysiology of chronic anxiety states. These cellular changes may lead to an increased vulnerability to stress- and anxiety-related responses in adulthood.

Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems.

Our previous studies have shown that post-weaning social isolation of male rats leads to sensitization of serotonergic systems and increases in anxiety-like behavior in adulthood. Although studies in humans suggest that females have an increased sensitivity to stress and risk for the development of neuropsychiatric illnesses, most studies involving laboratory rats have focused on males while females have been insufficiently studied. The objective of this study was to investigate the effects of post-weaning social isolation on subsequent responses of an anxiety-related dorsal raphe nucleus (DR)-basolateral amygdala system to pharmacological challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142; a partial inverse agonist at the benzodiazepine allosteric site on the γ-aminobutyric acid (GABA)(A) receptor). Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-reared for an additional 2 weeks. We then used dual immunohistochemical staining for c-Fos and tryptophan hydroxylase in the DR or single immunohistochemical staining for c-Fos in the basolateral amygdala. Isolation-reared rats, but not group-reared rats, injected with FG-7142 had increased c-Fos expression within the basolateral amygdala and in serotonergic neurons in the dorsal, ventrolateral, caudal and interfascicular parts of the DR relative to appropriate vehicle-injected control groups. These data suggest that post-weaning social isolation of female rats sensitizes a DR-basolateral amygdala system to stress-related stimuli, which may lead to an increased sensitivity to stress- and anxiety-related responses in adulthood.