Effect of WAY-100135 on the hippocampal acetylcholine release potentiated by 8-OH-DPAT, a serotonin,, receptor agonist, in normal and p-chlorophenylalanine-treated rats as measured by in vivo microdialysis

Katsuhiko Nakai, Takeshi Fujii, Kazuko Fujimoto, Takeshi Suzuki, Koichiro Kawashima

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The mechanisms involved in the enhancement of acetylcholine (ACh) release in the rat hippocampus by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a serotonin (5-HT)(1A) receptor agonist, were investigated using in vivo microdialysis. Administration of p-chlorophenylalanine (PCPA, 300 mg/kg, i.p.), a tryptophan hydroxylase inhibitor, 3 days before the dialysis experiments reduced the hippocampal 5-HT content to 30% of that in saline-treated rats, but did not affect basal ACh release in the hippocampus. 8-OH-DPAT administered systemically (0.5 mg/kg, s.c.) or applied locally (30 μM) into the hippocampus through the dialysis probe significantly enhanced the release of ACh in the hippocampus of PCPA-treated rats to the same degree as that in saline-treated rats. Pretreatment with (+)WAY-100135 (5 mg/kg, i.p.), a selective 5-HT)(1A) receptor antagonist, completely eliminated the enhancement of ACh release induced by locally applied 8-OH-DPAT, but only partially reduced the effects induced by systemically administered 8-OH-DPAT, in both groups of rats. Systemically administered 8-OH-DPAT induced hyperlocomotion in the both saline- and PCPA-treated rats, but this was not eliminated by (+)WAY-100135. 8-OH-DPAT applied locally into the hippocampus did not elicit hyperlocomotion in either group of rats. These results suggest that the modification of endogenous 5-HT release via the 5-HT)(1A) autoreceptor is not involved in the 8-OH-DPAT-induced increase of hippocampal ACh release, and that the increase of ACh release induced by locally applied 8-OH-DPAT involves mainly hippocampal postsynaptic 5-HT)(1A) receptor stimulation. In addition, a possibility that subtypes of 5-HT receptors other than the 5-HT)(1A) receptor, probably 5-HT7 receptor in the septum as well as postsynaptic 5-HT)(1A) receptor in the hippocampus, are involved in the increased hippocampal ACh release induced by systemically administered 8-OH-DPAT is discussed.

Original languageEnglish
Pages (from-to)23-29
Number of pages7
JournalNeuroscience Research
Issue number1
Publication statusPublished - 1998 May 1



  • (+)WAY-100135
  • 8-hydroxy-2-(di-n-propylamino)tetralin
  • Acetylcholine
  • Hippocampus
  • Microdialysis
  • Radioimmunoassay
  • Serotonin(1A) receptor

ASJC Scopus subject areas

  • Neuroscience(all)

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