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.

Adolescence is a complex developmental period characterized by sexual and brain maturation. Stress during adolescence, as abandonment and social isolation, interferes with maturation of higher brain functions such as decision making, learning and memory. Since rats are social animals, we investigate the consequences of housing rats individually during adolescence on the development of addictive behaviors. From postnatal day 23 (weaning), male and female rats were either housed in groups of the same sex or single housed throughout the experiments. At day 35 they were tested for their locomotor response to cocaine (15 mg/kg). Our results indicate that isolation during adolescence increases the locomotor response to cocaine in drug‐naive female rats. Unlike females rats, isolation during the adolescence does not affect the initial locomotor response to cocaine in males. However, these prepubertal males that normally do not show cocaine sensitization at this age, sensitized to cocaine when reared in isolation during adolescence. These results show that rearing rats in isolation exacerbates the behavioral effects of cocaine, and that the effect varies according to the sex of the animal. They also advocate for closer monitoring of neglected and solitary adolescents since they may be at a higher risk to develop drug dependency.Support or Funding InformationThis work supported by NSF under grant #OISE1545803.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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