Inhibition by MK-801 of morphine-induced conditioned place preference and postsynaptic dopamine receptor supersensitivity in mice.
Intraperitoncel injection of morphine (5 mg/kg) in mice every other day for 8 days produced conditioned place preference (CPP). CPP effects were evaluated by assessing the difference in time spent in the drug-paired compartment and the saline-paired compartment of the place conditioning apparatus. The injection of a noncompetitive NMDA antagonist, MK-801 (0.05 and 0.1 mg/kg. IP), prior to and during morphine treatment in mice inhibited morphine-induced CPP. The development of postsynaptic dopamine (DA) receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg). MK-801 inhibited that development of postsynaptic DA receptor supersensitivity. MK-801 also inhibited apomorphine-induced climbing behavior, suggesting that MK-801 inhibits dopaminergic activation mediated via the NMDA receptor. These results suggest that the development of morphine-induced CPP may be associated with the development of postsynaptic DA receptor supersensitivity. The development of morphine-induced CPP and DA receptor supersensitivity may be closely related to NMDA receptor-mediated dopaminergic activity, because morphine-induced changes in sensitivity to apomorphine, as well as apomorphine-induced climbing behavior in morphine treated mice, were both blocked by MK-801.
Kim
H S
HS
Department of Pharmacology, College of Pharmacy, Chungbuk National University, Korea.
Jang
C G
CG
Park
W K
WK
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects
D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D011954:Receptors, Dopamine; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; D009020:Morphine; D001058:Apomorphine