Bell J A, Beglan C L
Neuroimaging and Drug Action Section, Division of Intramural Research, National Institute on Drug Abuse, Baltimore, MD 21224, USA.
Eur J Pharmacol. 1995 Dec 27;294(1):289-96. doi: 10.1016/0014-2999(95)00547-1.
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.
