Ontogeny of NMDA receptor-mediated morphine tolerance in the postnatal rat.
N-methyl-D-aspartate (NMDA) receptor antagonists are effective in inhibiting the development of morphine tolerance in adult rats. But NMDA receptors undergo dramatic change during the first few weeks of the postnatal life in the rat, and it is unknown whether NMDA receptor antagonists can inhibit the acquisition of opiate tolerance in the developing organism. Here, we investigated the effects of two NMDA receptor antagonists MK-801 and dextromethorphan on the development of morphine tolerance in 7-, 14-, and 21-day-old rats. NMDA receptor antagonists are not effective in attenuating morphine tolerance in the neonatal rat whereas they were partially effected in the 14-day-old and fully effective in rats as old or older than 21 days of age. These data suggest that there exists a transition age, around the second postnatal week in the rat, for the NMDA receptor to play a role in the development of morphine tolerance.
Zhu
Hongbo
H
Biopsychology Doctoral Program, Department of Psychology, Hunter College, City University of New York, 695 Park Avenue, New York, NY 10021, USA Division of Developmental Psychobiology, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Barr
Gordon A
GA
D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine