Fentanyl self-administration in juvenile rats that were tolerant and dependent to fentanyl as infants

Human neonates and infants can become tolerant and dependent during continuous fentanyl or morphine administration. The long-term consequences in these individuals as juveniles and adults are unknown. This study compared fentanyl self-administration behavior in juvenile rats that were opioid naive or were exposed chronically to fentanyl as infants. Postnatal day 14 infant rats remained naive or were implanted with saline- or fentanyl-filled Alzet minipumps. After 72 h, fentanyl's antinociceptive potency was 3.0-fold lower in the fentanyl-infused rats. Naloxone precipitated withdrawal occurred only in the fentanyl-infused animals. Other similarly treated infant rats were allowed to mature into P42 juvenile rats before enrolling them in an oral fentanyl self-administration study. Rats from each group consumed significantly more fentanyl than quinine. However, those rats, tolerant and dependent to fentanyl as infants, did not self-administer more fentanyl than their opiate-naive littermates. The issue of whether fentanyl was consumed for its reinforcing properties was demonstrated when noncontingent administration of opiate antagonists significantly reduced fentanyl intake in another group of juvenile rats. These data indicate that fentanyl is consumed for its reinforcing properties, but that infant fentanyl tolerance and dependence did not predispose them to self-administer more fentanyl than opiate-naive animals.