Stressful environmental and social stimulation in adolescence causes antidepressant-like effects associated with epigenetic induction of the hippocampal BDNF and mossy fibre sprouting in the novelty-seeking phenotype.

An outbred rat model of novelty-seeking phenotype can differentiate between rats that show high rates (high responders; HRs) versus low rates (low responders; LRs) of locomotor reactivity to a novel environment. In the present study, LR and HR rats were exposed to a regimen of environmental and social stimuli (ESS) consisting of 14 random exposures of isolation, crowding or novel environment, once per day during the peripubertal-juvenile period (postnatal days 28-41) or handled as controls. Twenty-four hours after the last ESS exposure or control handling, all animals were tested on the forced swim and social interaction tests for depressive-like and social anxiety-like behaviors respectively. The ESS exposure during the peripubertal-juvenile period led to antidepressive-like effects on the forced swim test associated with increase in acetylation of histones 3 and 4 at the promoter regions P2 and P4 of the brain-derived neurotrophic factor (BDNF) gene in the dorsal hippocampus of HRs. Moreover, epigenetic activation of the hippocampal BDNF in the HRs following ESS exposure was accompanied by increase in the supra-pyramidal mossy fibre (SP-MF) and total mossy fibre terminal field volumes compared to handled controls. These findings suggest that the ESS exposure in the peripubertal-juvenile period may constitute an example of environmental induction of the hippocampal BDNF, and may mimic behavioral effects of exogenous antidepressants in the HR phenotype. Published by Elsevier Ireland Ltd.