Does dizocilpine (MK-801) inhibit the development of morphine-induced behavioural sensitization in rats?
Intermittent morphine pretreatment (10 mg/kg/day for 14 days) induced long-lasting (one month post-treatment) sensitization to the locomotor effects of morphine and amphetamine in rats. Co-administration of the non-competitive NMDA-receptor antagonist dizocilpine (MK-801) (0.1 mg/kg) with morphine did not prevent the development of long-term behavioural sensitization. However, this dose of MK-801 did cause long-term sensitization to its own locomotor effects. Co-administration of 0.25 mg/kg MK-801 with morphine caused death in 60% of the animals. In the animals that survived MK-801 plus morphine pretreatment, neither short-term (3 days) nor long-term morphine-induced sensitization was observed. MK-801 alone (0.25 mg/kg/day for 14 days) induced short-term cross-sensitization to morphine. Thus, the development of long-term morphine-induced locomotor sensitization could only be prevented by a dose of MK-801 that yields a lethal combination with morphine. In addition, MK-801 induced sensitization to its own locomotor effects and cross-sensitization to morphine. These findings seriously question whether MK-801 can be used to study the development of morphine-induced behavioural sensitization.
Vanderschuren
L J
LJ
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Faculty of Medicine, Amsterdam, The Netherlands. ljmj.vanderschuren.pharm@med.vu.nl
Schoffelmeer
A N
AN
De Vries
T J
TJ
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; D009294:Narcotics; D016291:Dizocilpine Maleate; D009020:Morphine; D000661:Amphetamine