Inhibition by MK-801 of cocaine-induced sensitization, conditioned place preference, and dopamine-receptor supersensitivity in mice.
Repeated administration of cocaine led to increases in ambulation-accelerating activity (sensitization) and conditioned place preference (CPP). Dopamine (DA)-receptor supersensitivity was also developed in cocaine-induced sensitized and CPP mice. An N-methyl-D-aspartate (NMDA)-receptor antagonist, MK-801, blocked simultaneously developments of cocaine-induced behavioral sensitization, CPP, and DA-receptor supersensitivity. Furthermore, MK-801 inhibited a apomorphine-induced striatal dopaminergic action: climbing behavior. These results suggest that the cocaine-induced dopaminergic behaviors such as sensitization to ambulatory activity and CPP may be produced via activation of the NMDA receptor. The development of postsynaptic DA-receptor supersensitivity may be an underlying common mechanism that mediates cocaine-induced behavioral sensitization and CPP.
Kim
H S
HS
Department of Pharmacology, College of Pharmacy, Chungbuk National University, Cheongju, Korea.
Park
W K
WK
Jang
C G
CG
Oh
S
S
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000037:antagonists & inhibitors*; D003216:Conditioning, Operant / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009292:Narcotic Antagonists / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D011954:Receptors, Dopamine; D016291:Dizocilpine Maleate; D003042:Cocaine; D001058:Apomorphine