Phencyclidine increases vesicular dopamine uptake.
Phencyclidine (PCP) rapidly (within 1 h) increased vesicular dopamine uptake and binding of the vesicular monoamine transporter-2 (VMAT-2) ligand, dihydrotetrabenazine. Uptake returned to basal values 3 h in the striatum after a high-dose administration of this drug (15 mg/kg i.p.). In contrast, a similar pretreatment with another non-competitive NMDA receptor antagonist, dizocilpine;([5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine; MK-801; 1 mg/kg, i.p.), was without effect on vesicular dopamine uptake. Pretreatment with the dopamine D2 receptor antagonist, eticlopride, blocked the increase in vesicular dopamine uptake caused by PCP administration. These data demonstrate a heretofore unreported mechanism that may contribute to the ability of PCP to influence dopamine neuronal function and exert its pharmacological effects.
Crosby
Michael J
MJ
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East, Salt Lake City, UT 84112, USA.
Hanson
Jarom E
JE
Fleckenstein
Annette E
AE
Hanson
Glen R
GR
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000493:pharmacokinetics*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology; D013572:Synaptic Vesicles / Q000187:drug effects* / Q000378:metabolism; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D014316:Tritium
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D012457:Salicylamides; D014316:Tritium; C032811:dihydrotetrabenazine; D016291:Dizocilpine Maleate; D010622:Phencyclidine; C045989:eticlopride; D004298:Dopamine; D013747:Tetrabenazine