Impact of Cesarean Delivery on Reward Behavior and Neurodevelopment in Adult Prairie Vole Offspring

Accumulating clinical evidence has shown that birth by Cesarean section (CS) is associated with a higher incidence of disorders involving the dysregulation of dopamine (DA), such as attention deficit-hyperactivity disorder, autism spectrum disorder, and obesity, compared to vaginal delivery (VD). The mesolimbic (ML) system encompasses DAergic neurons that modulate reward processes underlying learning, motivation, and food intake. Previous research has shown that there are lower levels of DA in the prefrontal cortex and higher in the nucleus accumbens (NAc) of CS offspring. Alterations in the ML-DA system as a consequence of birth via CS may impact behavioral response to rewarding stimuli, such as food. Thus, we aimed to ascertain the behavioral and neurodevelopmental outcomes relevant to food reward in CS prairie vole offspring. This study utilized conditioned place preference (CPP) testing to assess learning using context-dependent conditioning, operant conditioning to assess acquisition of a conditioned response and motivation to receive a reinforcer, and immunohistochemistry (IHC) to stain for tyrosine hydroxylase (TH) in the NAc. Behavioral results showed no difference in preference for the conditioned chamber during CPP testing between CS offspring and their VD counterparts. CS prairie vole offspring had a lower average break point during progressive-ratio testing compared to VD offspring, but no difference in response during fixed-ratio 1 or 3 testing. IHC results showed CS offspring had lower levels of TH-immunoreactivity in the NAc core and shell. These findings further support that delivery by CS has long-term neurodevelopmental effects, specifically in the brain's reward system, and that CS offspring have decreased motivation toward food reward independent of deficits in learning.