dizocilpine-maleate and dihydrotetrabenazine

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.

Topics: Animals; Binding, Competitive; Dizocilpine Maleate; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Male; Phencyclidine; Rats; Rats, Sprague-Dawley; Salicylamides; Synaptic Vesicles; Tetrabenazine; Tritium