Evidence for 5-HT4 receptor involvement in the enhancement of acetylcholine release by p-chloroamphetamine in rat frontal cortex.
The roles of endogenous serotonin (5-HT) and 5-HT receptor subtypes in regulation of acetylcholine (ACh) release in frontal cortex of conscious rats were examined using a microdialysis technique. Systemic administration (1 and 3 mg/kg, i.p.) of the 5-HT-releasing agent p-chloroamphetamine (PCA) elevated ACh output in a dose-dependent manner. Depletion of endogenous 5-HT by p-chlorophenylalanine significantly attenuated the facilitatory effect of PCA on ACh release. The PCA (3 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (10 mg/kg, i.p.; 100 microM), 5-HT(1A/1B)/beta-adrenoceptor antagonists (-)-pindolol (8 mg/kg, i.p.) and (-)-propranolol (150 microM), 5-HT(2A/2C) antagonist ritanserin (1 mg/kg, i.p.; 10 microM) and 5-HT3 antagonist ondansetron (1 mg/kg, i.p.; 10 microM) failed to significantly modify the effect of PCA. These results suggest that PCA-induced enhancement of 5-HT transmission facilitates ACh release from rat frontal cortex at least in part through 5-HT4 receptors.
Yamaguchi
T
T
Department of Pharmacology, Clinical Pharmacology Research Laboratory, Yamanouchi Pharmaceutical Co. Ltd., Tokyo, Japan. yamagu_t@yamanouchi.co.jp
Suzuki
M
M
Yamamoto
M
M
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D011985:Receptors, Serotonin; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D010133:p-Chloroamphetamine; D000109:Acetylcholine