Demonstration of the facilitatory role of 8-OH-DPAT on cholinergic transmission in the rat hippocampus using in vivo microdialysis.
The role of the serotonin (5-HT)1A receptor in the regulation of acetylcholine (ACh) release in the hippocampus was investigated using an in vivo microdialysis technique and a sensitive radioimmunoassay specific for ACh. The mean (+/- S.E.M.) basal ACh contents in the hippocampal perfusate of conscious, freely moving rats was 60 +/- 4 (n = 29) and 3691 +/- 265 fmol/30 min (n = 31), respectively, in the absence and presence of physostigmine (Phy) in the perfusion fluid. Systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.5 mg/kg, s.c.), a 5-HT1A agonist, significantly enhanced ACh release both in the presence and absence of Phy. Local application of 8-OH-DPAT (3-30 microM) into the hippocampus through the microdialysis probe significantly potentiated ACh release only in the presence of Phy, whereas no significant effect was observed in its absence. Pretreatment with NAN-190 (3 mg/kg, i.p.), a 5-HT1A antagonist, eliminated the increasing effect of systemically applied 8-OH-DPAT on ACh release, while NAN-190 alone had no effect on basal ACh release either in the absence or presence of Phy. Consistent with the time course of ACh release, systemic administration of 8-OH-DPAT evoked hyperlocomotion, which was reversed by NAN-190. However, local hippocampal application of 8-OH-DPAT did not affect the locomotor activity of the rats. These findings suggest that at least two different sites are involved in the 8-OH-DPAT-induced increase in the release of ACh in the rat hippocampus in vivo.
Fujii
T
T
Department of Pharmacology, Kyoritsu College of Pharmacy, Minato-ku, Tokyo, Japan.
Yoshizawa
M
M
Nakai
K
K
Fujimoto
K
K
Suzuki
T
T
Kawashima
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D010830:Physostigmine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000502:physiology; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*
D002800:Cholinesterase Inhibitors; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010830:Physostigmine; D000109:Acetylcholine