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CP-135,807, a Selective 5-HT1D Agonist: Effects in Drug Discrimination and Punishment Procedures in the Pigeon

CP-135,807, a Selective 5-HT1D Agonist: Effects in Drug Discrimination and Punishment Procedures in the Pigeon

R S Mansbach, C C Rovetti, J E Macor

Psychopharmacology (Berl). 1996 Dec;128(3):313-9.

PMID: 8972551

Abstract:

CP-135,807 [3-(N-methylpyrrolidin-2R-ylmethyl)-5-(3-nitropyrid-2- yl)amino-1H-indole] binds with high affinity to central 5-HT1D receptors, and in functional studies produces dose-dependent decreases in extracellular serotonin. These and other findings have suggested that CP-135,807 may act as a terminal 5-HT autoreceptor agonist. In an attempt to characterize the behavioral activity of selective 5-HT1D ligands, adult male Carneau pigeons were trained to discriminate IM injections of 0.1 mg/kg CP-135,807 from saline under a two-key, fixed ratio schedule of food-reinforced key pecking. CP-135,807 and the structurally unrelated 5-HT1D agonist CP-286,601 fully and dose-dependently substituted for the training dose. In contrast, little substitution was observed following administration of 8-OH-DPAT, a potent 5-HT1A agonist, the 5-HT1B agonist CP-94,253, or the serotonin reuptake inhibitor sertraline. In addition, the discriminative stimulus produced by CP-135,807 was not blocked by WAY 100,635, a selective 5-HT1A antagonist, but was completely and dose-dependently antagonized by the selective 5-HT1D antagonist, GR 127935. In subjects trained under a multiple schedule of punished and unpunished responding, 8-OH-DPAT produced large increases in punished responding while having little effect on unpunished responding. In contrast, CP-135,807 and CP-94,253 produced no antipunishment effects, while GR 127935 produced modest increases in punished responding. Collectively, these results suggest that CP-135,807 produces centrally mediated psychoactive effects that differ distinctly from those of 5-HT1A agonists.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP151272901	CP-135807		151272-90-1	Price

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