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Vol. 292, Issue 3, 1111-1117, March 2000

Regulation of Extracellular Concentrations of 5-Hydroxytryptamine (5-HT) in Mouse Striatum by 5-HT1A and 5-HT1B Receptors1

Deborah A. Knobelman, Hank F. Kung and Irwin Lucki

Departments of Pharmacology (D.A.K., H.F.K., I.L.), Radiology (H.F.K.), and Psychiatry (I.L.), University of Pennsylvania, Philadelphia, Pennsylvania

The ability of selective serotonin (5-HT) receptor agonists to reduce the extracellular concentration of 5-HT was examined in the striatum of awake, unrestrained mice by in vivo microdialysis. Systemic administration of either 8-OH-PIPAT {R-(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3'-iodo-2'-propenyl)] aminotetralin}, a novel 5-HT1A receptor agonist, or CP 94,253, a selective 5-HT1B receptor agonist, resulted in significant dose-related reductions of striatal 5-HT. The effect of 8-OH-PIPAT (1.0 mg/kg) was blocked by pretreatment with WAY 100635 (0.1 mg/kg), a selective 5-HT1A receptor antagonist, but it was not blocked by pretreatment with GR 127935 (0.056 mg/kg), a selective 5-HT1B/1D receptor antagonist. The effect of CP 94,253 (1.0 mg/kg) was blocked by pretreatment with GR 127935 (0.056 mg/kg) but was not blocked by pretreatment with WAY 100635 (0.1 mg/kg). Neither WAY 100635 nor GR 127935 altered extracellular 5-HT levels at the doses that were able to completely block the effects of either 8-OH-PIPAT or CP 94,253. The present findings suggest that, on systemic administration, both 8-OH-PIPAT and CP 94,253 are potent and selective agonists at the somatodendritic 5-HT1A autoreceptor and terminal 5-HT1B/1D autoreceptor, respectively, and are each able to cause decreases in extracellular levels of 5-HT in the mouse striatum by activating a distinct set of receptors.

1 This research was supported by U.S. Public Health Service Grant MH 48125 and predoctoral National Research Service Award Grant MH 12147 (to D.A.K.).

0022-3565/00/2923-1111$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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