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 continu ous fentanyl or morphine administration. The long-term consequences in thes e individuals as juveniles and adults are unknown. This study compared fent anyl self-administration behavior in juvenile rats that were opioid naive o r were exposed chronically to fentanyl as infants. Postnatal day 14 infant rats remairied naive or were implanted with saline- or fentanyl-filled Alze t minipumps. After 72 h, fentanyl's antinociceptive potency was 3.0-fold lo wer 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 o ral fentanyl self-administration study. Rats from each group consumed signi ficantly more fentanyl than quinine. However, those rats, tolerant and depe ndent to fentanyl as infants, did not self-administer more fentanyl than th eir opiate-naive littermates. The issue of whether fentanyl was consumed fo r its reinforcing properties was demonstrated when noncontingent administra tion 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 dependen ce did not predispose them to self-administer more fentanyl than opiate-nai ve animals. (C) 2000 Elsevier Science Inc.