Increased social reward behavior in adolescent male and female rats exposed prenatally to alcohol is associated with altered dopamine receptor expression.

Prenatal alcohol exposure (PAE) has detrimental consequences on cognitive, physiological, and social development. Adolescence, characterized by increased exploration, risk-taking, and social interaction, is a critical developmental stage that may amplify social deficits caused by PAE. This study examined how PAE affects social motivation in males and females across adolescent development using a social reward task to measure preferences for social and non-social stimuli at postnatal day (P)30, P40, P50, and P70. Our results demonstrated that PAE rats exhibited higher social motivation than controls during training and progressive ratio sessions. Extinction testing showed PAE males persisted in responding to the previously social side, resisting the typical shift to a non-social preference observed in controls. Dopamine receptor analysis revealed sex- and age-specific effects. Both PAE males and females showed increased D2 receptor expression in the nucleus accumbens (NAcc) at P30 and P50. In contrast, D3 receptor expression was decreased in the NAcc of P30 PAE males. In the medial amygdala, PAE females exhibited reduced D3 expression at P40 and P70, while PAE males showed similar reductions at P30 and P50. These findings suggest that PAE disrupts development of social motivation and dopamine receptor expression, with distinct effects based on sex and developmental stage. The observed increases in D2 expression, coupled with decreases in the inhibitory D3 receptor, may contribute to the heightened social motivation in PAE rats by shifting the balance of dopamine signaling toward increased reward sensitivity and reduced behavioral inhibition.