Effect of dopaminergic drugs on enhancement of the binding of quinuclidinyl benzilate by phencyclidine in vivo.
Phencyclidine has been shown to enhance the specific binding of [3H]quinuclidinyl benzilate (QNB) in the brain of the mouse when both compounds are given in vivo. Since a variety of studies indicate that dopaminergic (DA) systems are involved in the action of phencyclidine, it seemed that DA systems might mediate the enhancement of the binding of QNB by phencyclidine. The results of the present studies demonstrate that the neurotoxin 6-hydroxydopamine, the DA D1 antagonist (R)-8-[chloro]-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1-H-3-benzazepine-7- ol) (SCH23390), the DA D1 agonist p-dibenzylamino benzonitrile (SKF38393) and the DA D2 antagonist spiperone, all failed to modify the ability of phencyclidine to enhance the accumulation of QNB in brain. Quinpirole, a DA D2 agonist diminished accumulation of QNB after phencyclidine, however, this effect was confounded by quinpirole decreasing the non-specific binding of QNB, as well as increasing concentrations of QNB in plasma, when given with phencyclidine. In contrast, haloperidol, a DA antagonist, decreased the enhanced specific binding of QNB after phencyclidine without any apparent confounding influences. Since haloperidol is also known to strongly inhibit the binding of ligands to the sigma receptors, it was hypothesized that the actions of phencyclidine and haloperidol on the binding of QNB in vivo may be through sigma receptors rather than DA systems.
Boggan
W O
WO
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425-0742.
Middaugh
L D
LD
Faught
K
K
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D006892:Hydroxydopamines / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010622:Phencyclidine / Q000494:pharmacology*; D019257:Quinpirole; D011812:Quinuclidines; D011813:Quinuclidinyl Benzilate
D001552:Benzazepines; D015259:Dopamine Agents; D004873:Ergolines; D006892:Hydroxydopamines; D011812:Quinuclidines; D019257:Quinpirole; D011813:Quinuclidinyl Benzilate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001285:Atropine; D016627:Oxidopamine; D010622:Phencyclidine; D004298:Dopamine; D009638:Norepinephrine