TY - JOUR
T1 - 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
AU - Nakai, Katsuhiko
AU - Fujii, Takeshi
AU - Fujimoto, Kazuko
AU - Suzuki, Takeshi
AU - Kawashima, Koichiro
N1 - Funding Information:
We are grateful to Ms. Miki Sugiyama and Ms. Mioko Banno for technical assistance. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan.
PY - 1998/5
Y1 - 1998/5
N2 - 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.
AB - 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.
KW - (+)WAY-100135
KW - 8-hydroxy-2-(di-n-propylamino)tetralin
KW - Acetylcholine
KW - Hippocampus
KW - Microdialysis
KW - Radioimmunoassay
KW - Serotonin(1A) receptor
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UR - http://www.scopus.com/inward/citedby.url?scp=0031841180&partnerID=8YFLogxK
U2 - 10.1016/S0168-0102(98)00019-4
DO - 10.1016/S0168-0102(98)00019-4
M3 - Article
C2 - 9704975
AN - SCOPUS:0031841180
VL - 31
SP - 23
EP - 29
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 1
ER -