Social isolation of adolescent male rats increases anxiety and K+ -induced dopamine release in the nucleus accumbens: Role of CRF-R1.

Early life adversity can disrupt development leading to emotional and cognitive disorders. This study investigated the effects of social isolation after weaning on anxiety, body weight and locomotion, and on extracellular dopamine (DA) and glutamate (GLU) in the nucleus accumbens (NAc) and their modulation by corticotropin releasing factor receptor 1. On the day of weaning, male rats were housed singly or in groups for 10 consecutive days. Anxiety-like behaviors were assessed by an elevated plus maze (EPM) and an open field test (OF). Neurotransmitter levels were measured by in vivo microdialysis. Single-housed rats spent less time, and entered more, into the closed arms of an EPM than group-housed rats. They also spent less time in the center of an OF, weighed more and showed greater locomotion. In the NAc, no differences in CRF, or in basal extracellular DA or GLU between groups, were observed. A depolarizing stimulus increased DA release in both groups but to higher levels in isolated rats, whereas GLU increased only in single-housed rats. Blocking CRF-R1 receptors with CP-154,526 decreased DA release in single-housed but not in group-housed rats. The corticotropin releasing factor receptor type 1 receptor antagonist also decreased GLU in group-housed animals. These results show that isolating adolescent rats increases anxiety, body weight and ambulation, as well as the sensitivity of dopaminergic neurons to a depolarizing stimulus. This study provides further evidence of the detrimental effects of social isolation during early development and indicates that dysregulation of the CRF system in the NAc may contribute to the pathologies observed.