Abstract Body: Long-term effects on the cardiovascular system of offspring exposed to fentanyl in utero are one of the understudied aspects of the opioid crisis. Previously, we have shown that offspring exposed to opioids in utero display exacerbated somatic signs of withdrawal compared to vehicle-exposed offspring. We also showed that prenatal opioid exposure induce long lasting effects increasing blood pressure (BP) in the adult offspring. Buprenorphine (BUP) is one of the most effective FDA-approved standard-of-care therapies used to treat mothers with opioid use disorder and their newborns with neonatal opioid withdrawal syndrome (NOWS). Yet, long-term effects of BUP in the pediatric population is limited. This study aimed to determine the efficacy of BUP in reducing somatic signs of withdrawal in rat neonates and the long-term effects on BP control. Female Sprague-Dawley rat breeders were implanted with a chronic jugular vein catheter and subjected to 2-hr self-administration (SA) sessions of vehicle (VEH, 0.9% NaCl, n=3) or fentanyl (FEN, 2.5 μg/kg/infusion/lever press, n=3). After rats developed dependence, they were paired during proestrus with males for breeding. SA sessions continued until delivery. There were no changes in maternal weight gain and pup weights at birth. At postnatal day 1, a subset of FEN-SA pups was treated with BUP for 5 consecutive days (1 mg/kg, sc). Video recording was performed daily to quantify somatic signs of withdrawal, including body curls, head movements, and spasms. FEN-SA increased withdrawal at postnatal days 1-3. This effect was attenuated in FEN-SA offspring treated with BUP (p<0.05).14-week-old male offspring were implanted with radiotelemetry (n=4 per group). Compared to VEH-SA, FEN-SA offspring showed: 1) increased BP in response to phenylephrine (PE, 40 µg/kg ip), 2) tachycardic response to 1-hour restraint stress followed by impaired BP recovery (p<0.05, respectively), 3) similar acute responses to AngII (30 µg/kg, sc), 4) exacerbated BP and delayed heart rate recovery in response to acute FEN (20 µg/kg, sc, p<0.05), although plasma clearance was similar between groups. BUP treatment in FEN-SA offspring did not influence acute changes in BP or heart rate to different hypertensive stimuli. Taken together our data suggests that an opioid-based therapy effectively reduced somatic signs of withdrawal; however, it does not seem effective in attenuating the acute and chronic BP responses in prenatal fentanyl-exposed offspring.