Abstract
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.
Footnotes
-
Send reprint requests to: Dr. Irwin Lucki, University of Pennsylvania, Department of Psychiatry, 3600 Market St., Room 748, Philadelphia, PA 19104-2648. E-mail: lucki{at}pharm.med.upenn.edu
-
↵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.).
- Abbreviations:
- 5-HT
- serotonin
- 8-OH-DPAT
- 8-hydroxy-2-dipropylaminotetralin
- 8-OH-PIPAT
- R-(+)-trans-8-hydroxy-2-[N-n-propyl-N-(3′-iodo-2′-propenyl)] aminotetralin
- AUC
- area under the curve
- TFMPP
- N-(3-trifluoromethylphenyl)piperazine
- Received December 8, 1999.
- Accepted December 8, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|