MK-801 blocks the expression but not the development of tolerance to morphine in the isolated spinal cord of the neonatal rat.
This study investigated the role of (MK-801; [(+)-5-methyl-10,11-dihydro-5 H-dibenzo[a,d]-cyclo-hepten-5,10-imine hydrogen maleate) in the development and expression of tolerance to morphine in the isolated spinal cord of the neonatal rat. Neonatal rats were treated chronically (3 or 4 days) with either morphine, morphine + MK-801, MK-801 alone or saline. Morphine, in a concentration-dependent manner, depressed a delayed ventral root potential produced by supramaximal electrical stimulation of an ipsilateral dorsal root. Chronic treatment of neonates with morphine alone, morphine with MK-801 and MK-801 alone produced tolerance to morphine depression of the ventral root potential. Acute MK-801 (300 nM) did not depress the ventral root potential but enhanced the depressant effects of acute morphine on the ventral root potential in saline-treated controls. Acute MK-801 (300 nM) appeared to reverse tolerance in all of the drug-treated groups. We conclude that MK-801 can mask the expression of morphine tolerance by enhancing the acute depressant effects of morphine.
Bell
J A
JA
Neuroimaging and Drug Action Section, Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Beglan
C L
CL
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004361:Drug Tolerance; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects*
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate; D009020:Morphine