Developmental Programming of Adrenal Chromaffin Cell Connexin Plasticity by Neonatal Maternal Separation

Adrenal chromaffin cells are key effectors of the sympathoadrenal response and play a central role in physiological adaptation to stress. While acetylcholine and pituitary ad-enylate cyclase-activating polypeptide (PACAP) are recognized regulators of catechol-amine secretion, connexin-mediated gap junctional communication provides an addi-tional mechanism for coordinating chromaffin-cell activity. Whether early-life experience influences the capacity of chromaffin-cell networks to undergo stress-induced remodeling remains unknown. To address this question, we examined connexin 36 (Cx36) and connexin 43 (Cx43) expression in the adrenal medulla of adult rats exposed to neonatal maternal separation (MS; 3 h daily, postnatal days 2–15) and subsequently challenged with an 8-day unpredictable mild stress (UMS) protocol. Under basal adult conditions, MS did not alter adrenal medullary Cx36 or Cx43 immunoreactivity relative to ani-mal-facility-reared controls. In contrast, UMS increased connexin immunoreactivity, and this response was significantly enhanced in animals with a history of MS. MS+UMS animals also displayed augmented corticosterone responses to acute restraint stress, particularly in females. These findings indicate that neonatal maternal separation does not produce a constitutively altered adult chromaffin-cell phenotype but modifies the mag-nitude of subsequent stress-induced adrenal remodeling.